Abstract
Chromatin is a dynamic and highly organised structure that plays a role in all aspects of chromatin biology and controls access to DNA. The basic repeating unit of chromatin is the nucleosome, an octamer of histone proteins wrapped around twice with DNA. Transcriptional gene regulation is largely controlled by the epigenetic regulation of the nucleosome, both through the position of the nucleosome in the DNA and chemical modifications to the histone proteins within the nucleosome core. In this chapter, we discuss the role of the nucleosome in controlling gene regulation at promoters, enhancers and in gene bodies. We also discuss the role of bivalent chromatin and asymmetric nucleosomes at these elements. While the focus of this chapter is on transcriptional regulation, many of the concepts also extend to other aspects of chromatin biology including DNA repair and replication.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adams-Cioaba MA, Min J (2009) Structure and function of histone methylation binding proteins. Biochem Cell Biol 87(1):93–105
Adhikary S, Sanyal S, Basu M, Sengupta I, Sen S, Srivastava DK et al (2016) Selective recognition of H3.1K36 dimethylation/H4K16 acetylation facilitates the regulation of all-trans-retinoic Acid (ATRA)-responsive genes by putative chromatin reader ZMYND8. J Biol Chem 291(6):2664–2681
Ai X, Parthun MR (2004) The nuclear Hat1p/Hat2p complex: a molecular link between type B histone acetyltransferases and chromatin assembly. Mol Cell 14(2):195–205
Allan RS, Zueva E, Cammas F, Schreiber HA, Masson V, Belz GT et al (2012) An epigenetic silencing pathway controlling T helper 2 cell lineage commitment. Nature 487(7406):249–253
Allfrey VG, Faulkner R, Mirsky AE (1964) Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc Natl Acad Sci U S A 51:786–794
Altaf M, Auger A, Monnet-Saksouk J, Brodeur J, Piquet S, Cramet M et al (2010) NuA4-dependent acetylation of nucleosomal histones H4 and H2A directly stimulates incorporation of H2A.Z by the SWR1 complex. J Biol Chem 285(21):15966–15977
Andersson R, Enroth S, Rada-Iglesias A, Wadelius C, Komorowski J (2009) Nucleosomes are well positioned in exons and carry characteristic histone modifications. Genome Res 19(10):1732–1741
Andreu-Vieyra C, Lai J, Berman BP, Frenkel B, Jia L, Jones PA et al (2011) Dynamic nucleosome-depleted regions at androgen receptor enhancers in the absence of ligand in prostate cancer cells. Mol Cell Biol 31(23):4648–4662
Arnold CD, Gerlach D, Stelzer C, Boryn LM, Rath M, Stark A (2013) Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 339(6123):1074–1077
Atsumi Y, Minakawa Y, Ono M, Dobashi S, Shinohe K, Shinohara A et al (2015) ATM and SIRT6/SNF2H mediate transient H2AX stabilization when DSBs form by blocking HUWE1 to allow efficient gammaH2AX foci formation. Cell Rep 13(12):2728–2740
Azuara V, Perry P, Sauer S, Spivakov M, Jorgensen HF, John RM et al (2006) Chromatin signatures of pluripotent cell lines. Nat Cell Biol 8(5):532–538
Banine F, Bartlett C, Gunawardena R, Muchardt C, Yaniv M, Knudsen ES et al (2005) SWI/SNF chromatin-remodeling factors induce changes in DNA methylation to promote transcriptional activation. Cancer Res 65(9):3542–3547
Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21(3):381–395
Bannister AJ, Schneider R, Kouzarides T (2002) Histone methylation: dynamic or static? Cell 109(7):801–806
Bao X, Rubin AJ, Qu K, Zhang J, Giresi PG, Chang HY et al (2015) A novel ATAC-seq approach reveals lineage-specific reinforcement of the open chromatin landscape via cooperation between BAF and p63. Genome Biol 16:284
Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z et al (2007) High-resolution profiling of histone methylations in the human genome. Cell 129(4):823–837
Bateman JR, Johnson JE, Locke MN (2012) Comparing enhancer action in cis and in trans. Genetics 191(4):1143–1155
Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A (2009) An operational definition of epigenetics. Genes Dev 23(7):781–783
Bernhart SH, Kretzmer H, Holdt LM, Juhling F, Ammerpohl O, Bergmann AK et al (2016) Changes of bivalent chromatin coincide with increased expression of developmental genes in cancer. Sci Rep 6:37393
Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J et al (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125(2):315–326
Bert SA, Robinson MD, Strbenac D, Statham AL, Song JZ, Hulf T et al (2013) Regional activation of the cancer genome by long-range epigenetic remodeling. Cancer Cell 23(1):9–22
Biswas M, Voltz K, Smith JC, Langowski J (2011) Role of histone tails in structural stability of the nucleosome. PLoS Comput Biol 7(12):e1002279
Blow MJ, McCulley DJ, Li Z, Zhang T, Akiyama JA, Holt A et al (2010) ChIP-Seq identification of weakly conserved heart enhancers. Nat Genet 42(9):806–810
Bogdanovic O, Fernandez-Minan A, Tena JJ, de la Calle-Mustienes E, Hidalgo C, van Kruysbergen I et al (2012) Dynamics of enhancer chromatin signatures mark the transition from pluripotency to cell specification during embryogenesis. Genome Res 22(10):2043–2053
Bonn S, Zinzen RP, Girardot C, Gustafson EH, Perez-Gonzalez A, Delhomme N et al (2012) Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development. Nat Genet 44(2):148–156
Bulger M, Groudine M (2011) Functional and mechanistic diversity of distal transcription enhancers. Cell 144(3):327–339
Bultman SJ, Gebuhr TC, Magnuson T (2005) A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development. Genes Dev 19(23):2849–2861
Cajigas I, Leib DE, Cochrane J, Luo H, Swyter KR, Chen S et al (2015) Evf2 lncRNA/BRG1/DLX1 interactions reveal RNA-dependent inhibition of chromatin remodeling. Development 142(15):2641–2652
Calo E, Wysocka J (2013) Modification of enhancer chromatin: what, how, and why? Mol Cell 49(5):825–837
Caserta M, Agricola E, Churcher M, Hiriart E, Verdone L, Di Mauro E et al (2009) A translational signature for nucleosome positioning in vivo. Nucleic Acids Res 37(16):5309–5321
Champagne KS, Kutateladze TG (2009) Structural insight into histone recognition by the ING PHD fingers. Curr Drug Targets 10(5):432–441
Chang B, Chen Y, Zhao Y, Bruick RK (2007) JMJD6 is a histone arginine demethylase. Science 318(5849):444–447
Chang FT, Chan FL, JD RM, Udugama M, Mayne L, Collas P et al (2015) CHK1-driven histone H3.3 serine 31 phosphorylation is important for chromatin maintenance and cell survival in human ALT cancer cells. Nucleic Acids Res 43(5):2603–2614
Chen Y, Yang Y, Wang F, Wan K, Yamane K, Zhang Y et al (2006) Crystal structure of human histone lysine-specific demethylase 1 (LSD1). Proc Natl Acad Sci U S A 103(38):13956–13961
Chen HP, Zhao YT, Zhao TC (2015) Histone deacetylases and mechanisms of regulation of gene expression. Crit Rev Oncog 20(1-2):35–47
Choi JK (2010) Contrasting chromatin organization of CpG islands and exons in the human genome. Genome Biol 11(7):R70
Church M, Smith KC, Alhussain MM, Pennings S, Fleming AB (2017) Sas3 and Ada2(Gcn5)-dependent histone H3 acetylation is required for transcription elongation at the de-repressed FLO1 gene. Nucleic Acids Res 45(8):4413–4430
Clapier CR, Iwasa J, Cairns BR, Peterson CL (2017) Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nat Rev Mol Cell Biol 18(7):407–422
Creyghton MP, Markoulaki S, Levine SS, Hanna J, Lodato MA, Sha K et al (2008) H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell 135(4):649–661
Creyghton MP, Cheng AW, Welstead GG, Kooistra T, Carey BW, Steine EJ et al (2010) Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A 107(50):21931–21936
Dai HQ, Wang BA, Yang L, Chen JJ, Zhu GC, Sun ML et al (2016) TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling. Nature 538(7626):528–532
Dalvai M, Bellucci L, Fleury L, Lavigne AC, Moutahir F, Bystricky K (2013) H2A.Z-dependent crosstalk between enhancer and promoter regulates cyclin D1 expression. Oncogene 32(36):4243–4251
De S, Wurster AL, Precht P, Wood WH 3rd, Becker KG, Pazin MJ (2011) Dynamic BRG1 recruitment during T helper differentiation and activation reveals distal regulatory elements. Mol Cell Biol 31(7):1512–1527
Dhami P, Saffrey P, Bruce AW, Dillon SC, Chiang K, Bonhoure N et al (2010) Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution. PLoS One 5(8):e12339
Dovey OM, Foster CT, Cowley SM (2010) Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation. Proc Natl Acad Sci U S A 107(18):8242–8247
Edmunds JW, Mahadevan LC, Clayton AL (2008) Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation. EMBO J 27(2):406–420
Ellis SE, Gupta S, Moes A, West AB, Arking DE (2017) Exaggerated CpH methylation in the autism-affected brain. Molecular Autism 8:6
Ficz G, Branco MR, Seisenberger S, Santos F, Krueger F, Hore TA et al (2011) Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473(7347):398–402
Gaertner B, Johnston J, Chen K, Wallaschek N, Paulson A, Garruss AS et al (2012) Poised RNA polymerase II changes over developmental time and prepares genes for future expression. Cell Rep 2(6):1670–1683
Gal-Yam EN, Egger G, Iniguez L, Holster H, Einarsson S, Zhang X et al (2008) Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line. Proc Natl Acad Sci U S A 105(35):12979–12984
Ge Z, Wang H, Parthun MR (2011) Nuclear Hat1p complex (NuB4) components participate in DNA repair-linked chromatin reassembly. J Biol Chem 286(19):16790–16799
Gelfman S, Cohen N, Yearim A, Ast G (2013) DNA-methylation effect on cotranscriptional splicing is dependent on GC architecture of the exon-intron structure. Genome Res 23(5):789–799
Geyer PK, Green MM, Corces VG (1990) Tissue-specific transcriptional enhancers may act in trans on the gene located in the homologous chromosome: the molecular basis of transvection in Drosophila. EMBO J 9(7):2247–2256
Ghisletti S, Barozzi I, Mietton F, Polletti S, De Santa F, Venturini E et al (2010) Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity 32(3):317–328
Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S et al (2010) Distinct factors control histone variant H3.3 localization at specific genomic regions. Cell 140(5):678–691
Guo JU, Su Y, Shin JH, Shin J, Li H, Xie B et al (2014) Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nat Neurosci 17(2):215–222
Hahn MA, Wu X, Li AX, Hahn T, Pfeifer GP (2011) Relationship between gene body DNA methylation and intragenic H3K9me3 and H3K36me3 chromatin marks. PLoS One 6(4):e18844
Han P, Li W, Lin CH, Yang J, Shang C, Nuernberg ST et al (2014) A long noncoding RNA protects the heart from pathological hypertrophy. Nature 514(7520):102–106
Hassan AH, Prochasson P, Neely KE, Galasinski SC, Chandy M, Carrozza MJ et al (2002) Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell 111(3):369–379
He HH, Meyer CA, Shin H, Bailey ST, Wei G, Wang Q et al (2010) Nucleosome dynamics define transcriptional enhancers. Nat Genet 42(4):343–347
He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q et al (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333(6047):1303–1307
Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD et al (2007) Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39(3):311–318
Hesson LB, Sloane MA, Wong JW, Nunez AC, Srivastava S, Ng B et al (2014) Altered promoter nucleosome positioning is an early event in gene silencing. Epigenetics 9(10):1422–1430
Hinshelwood RA, Melki JR, Huschtscha LI, Paul C, Song JZ, Stirzaker C et al (2009) Aberrant de novo methylation of the p16INK4A CpG island is initiated post gene silencing in association with chromatin remodelling and mimics nucleosome positioning. Hum Mol Genet 18(16):3098–3109
Hodawadekar SC, Marmorstein R (2007) Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design. Oncogene 26(37):5528–5540
Hon GC, Hawkins RD, Ren B (2009) Predictive chromatin signatures in the mammalian genome. Hum Mol Genet 18(R2):R195–R201
Horton JR, Upadhyay AK, Qi HH, Zhang X, Shi Y, Cheng X (2010) Enzymatic and structural insights for substrate specificity of a family of jumonji histone lysine demethylases. Nat Struct Mol Biol 17(1):38–43
Hu G, Schones DE, Cui K, Ybarra R, Northrup D, Tang Q et al (2011) Regulation of nucleosome landscape and transcription factor targeting at tissue-specific enhancers by BRG1. Genome Res 21(10):1650–1658
Hu G, Cui K, Northrup D, Liu C, Wang C, Tang Q et al (2013) H2A.Z facilitates access of active and repressive complexes to chromatin in embryonic stem cell self-renewal and differentiation. Cell Stem Cell 12(2):180–192
Hu Z, Chen K, Xia Z, Chavez M, Pal S, Seol JH et al (2014) Nucleosome loss leads to global transcriptional up-regulation and genomic instability during yeast aging. Genes Dev 28(4):396–408
Huang H, Yu S, Liu H, Sun X (2012) Nucleosome organization in sequences of alternative events in human genome. Biosystems 109(2):214–219
Ichikawa Y, Connelly CF, Appleboim A, Miller TC, Jacobi H, Abshiru NA et al (2017) A synthetic biology approach to probing nucleosome symmetry. Elife 6:e28836
Ito S, D'Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y (2010) Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466(7310):1129–1133
Jeong KW, Kim K, Situ AJ, Ulmer TS, An W, Stallcup MR (2011) Recognition of enhancer element-specific histone methylation by TIP60 in transcriptional activation. Nat Struct Mol Biol 18(12):1358–1365
Jin C, Felsenfeld G (2007) Nucleosome stability mediated by histone variants H3.3 and H2A.Z. Genes Dev 21(12):1519–1529
Jin C, Zang C, Wei G, Cui K, Peng W, Zhao K et al (2009) H3.3/H2A.Z double variant-containing nucleosomes mark ‘nucleosome-free regions’ of active promoters and other regulatory regions. Nat Genet 41(8):941–945
Jin Q, Yu LR, Wang L, Zhang Z, Kasper LH, Lee JE et al (2011) Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation. EMBO J 30(2):249–262
John S, Sabo PJ, Johnson TA, Sung MH, Biddie SC, Lightman SL et al (2008) Interaction of the glucocorticoid receptor with the chromatin landscape. Mol Cell 29(5):611–624
Johnson CN, Adkins NL, Georgel P (2005) Chromatin remodeling complexes: ATP-dependent machines in action. Biochem Cell Biol 83(4):405–417
Jones PA (2012) Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 13(7):484–492
Kalakonda N, Fischle W, Boccuni P, Gurvich N, Hoya-Arias R, Zhao X et al (2008) Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1. Oncogene 27(31):4293–4304
Kawaguchi T, Tanigawa A, Naganuma T, Ohkawa Y, Souquere S, Pierron G et al (2015) SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies. Proc Natl Acad Sci U S A 112(14):4304–4309
Kelly TJ, Qin S, Gottschling DE, Parthun MR (2000) Type B histone acetyltransferase Hat1p participates in telomeric silencing. Mol Cell Biol 20(19):7051–7058
Kelly TK, Miranda TB, Liang G, Berman BP, Lin JC, Tanay A et al (2010) H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes. Mol Cell 39(6):901–911
Kelly TK, Liu Y, Lay FD, Liang G, Berman BP, Jones PA (2012) Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules. Genome Res 22(12):2497–2506
Kia SK, Gorski MM, Giannakopoulos S, Verrijzer CP (2008) SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF-INK4a locus. Mol Cell Biol 28(10):3457–3464
Kiefer CM, Hou C, Little JA, Dean A (2008) Epigenetics of beta-globin gene regulation. Mutat Res 647(1-2):68–76
Kim J, Daniel J, Espejo A, Lake A, Krishna M, Xia L et al (2006) Tudor, MBT and chromo domains gauge the degree of lysine methylation. EMBO Rep 7(4):397–403
Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J et al (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465(7295):182–187
Klose RJ, Zhang Y (2007) Regulation of histone methylation by demethylimination and demethylation. Nat Rev Mol Cell Biol 8(4):307–318
Koch F, Andrau JC (2011) Initiating RNA polymerase II and TIPs as hallmarks of enhancer activity and tissue-specificity. Transcription 2(6):263–268
Kolasinska-Zwierz P, Down T, Latorre I, Liu T, Liu XS, Ahringer J (2009) Differential chromatin marking of introns and expressed exons by H3K36me3. Nat Genet 41(3):376–381
Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4):693–705
Krebs AR, Karmodiya K, Lindahl-Allen M, Struhl K, Tora L (2011) SAGA and ATAC histone acetyl transferase complexes regulate distinct sets of genes and ATAC defines a class of p300-independent enhancers. Mol Cell 44(3):410–423
Kretzmer H, Bernhart SH, Wang W, Haake A, Weniger MA, Bergmann AK et al (2015) DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control. Nat Genet 47(11):1316–1325
Kriaucionis S, Heintz N (2009) The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324(5929):929–930
Ku M, Jaffe JD, Koche RP, Rheinbay E, Endoh M, Koseki H et al (2012) H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions. Genome Biol 13(10):R85
Kubik S, Bruzzone MJ, Jacquet P, Falcone JL, Rougemont J, Shore D (2015) Nucleosome stability distinguishes two different promoter types at all protein-coding genes in yeast. Mol Cell 60(3):422–434
Kundaje A, Kyriazopoulou-Panagiotopoulou S, Libbrecht M, Smith CL, Raha D, Winters EE et al (2012) Ubiquitous heterogeneity and asymmetry of the chromatin environment at regulatory elements. Genome Res 22(9):1735–1747
Kundu S, Ji F, Sunwoo H, Jain G, Lee JT, Sadreyev RI et al (2017) Polycomb repressive complex 1 generates discrete compacted domains that change during differentiation. Mol Cell 65(3):432–446. e5
Kwon H, Song K, Han C, Zhang J, Lu L, Chen W et al (2017) Epigenetic silencing of miRNA-34a in human cholangiocarcinoma via EZH2 and DNA methylation: impact on regulation of notch pathway. Am J Pathol 187(10):2288–2299
Laurette P, Strub T, Koludrovic D, Keime C, Le Gras S, Seberg H et al (2015) Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells. Elife 4:e06857
Lee J, Thompson JR, Botuyan MV, Mer G (2008) Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor. Nat Struct Mol Biol 15(1):109–111
Lee Y, Park D, Iyer VR (2017a) The ATP-dependent chromatin remodeler Chd1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes. Nucleic Acids Res 45(14):8646
Lee SM, Lee J, Noh KM, Choi WY, Jeon S, Oh GT et al (2017b) Intragenic CpG islands play important roles in bivalent chromatin assembly of developmental genes. Proc Natl Acad Sci U S A 114(10):E1885–E1e94
Leisegang MS, Fork C, Josipovic I, Richter FM, Preussner J, Hu J et al (2017) Long noncoding RNA MANTIS facilitates endothelial angiogenic function. Circulation 136(1):65–79
Levendosky RF, Sabantsev A, Deindl S, Bowman GD (2016) The Chd1 chromatin remodeler shifts hexasomes unidirectionally. Elife 5:e21356
Li Q, Zhou H, Wurtele H, Davies B, Horazdovsky B, Verreault A et al (2008) Acetylation of histone H3 lysine 56 regulates replication-coupled nucleosome assembly. Cell 134(2):244–255
Li XY, Thomas S, Sabo PJ, Eisen MB, Stamatoyannopoulos JA, Biggin MD (2011) The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding. Genome Biol 12(4):R34
Li L, Liu D, Bu D, Chen S, Wu J, Tang C et al (2013) Brg1-dependent epigenetic control of vascular smooth muscle cell proliferation by hydrogen sulfide. Biochim Biophys Acta 1833(6):1347–1355
Lin JC, Jeong S, Liang G, Takai D, Fatemi M, Tsai YC et al (2007) Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island. Cancer Cell 12(5):432–444
Lin JJ, Lehmann LW, Bonora G, Sridharan R, Vashisht AA, Tran N et al (2011) Mediator coordinates PIC assembly with recruitment of CHD1. Genes Dev 25(20):2198–2209
Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J et al (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271):315–322
Lo KA, Bauchmann MK, Baumann AP, Donahue CJ, Thiede MA, Hayes LS et al (2011) Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes. PLoS One 6(6):e19778
Lohr D, Tatchell K, Van Holde KE (1977) On the occurrence of nucleosome phasing in chromatin. Cell 12(3):829–836
Lu X, Simon MD, Chodaparambil JV, Hansen JC, Shokat KM, Luger K (2008) The effect of H3K79 dimethylation and H4K20 trimethylation on nucleosome and chromatin structure. Nat Struct Mol Biol 15(10):1122–1124
Luebben WR, Sharma N, Nyborg JK (2010) Nucleosome eviction and activated transcription require p300 acetylation of histone H3 lysine 14. Proc Natl Acad Sci U S A 107(45):19254–19259
Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389(6648):251–260
Maclary E, Hinten M, Harris C, Sethuraman S, Gayen S, Kalantry S (2017) PRC2 represses transcribed genes on the imprinted inactive X chromosome in mice. Genome Biol 18(1):82
Margaritis T, Holstege FC (2008) Poised RNA polymerase II gives pause for thought. Cell 133(4):581–584
Maurer-Stroh S, Dickens NJ, Hughes-Davies L, Kouzarides T, Eisenhaber F, Ponting CP (2003) The Tudor domain ‘Royal Family’: Tudor, plant Agenet, Chromo, PWWP and MBT domains. Trends Biochem Sci 28(2):69–74
May D, Blow MJ, Kaplan T, McCulley DJ, Jensen BC, Akiyama JA et al (2011) Large-scale discovery of enhancers from human heart tissue. Nat Genet 44(1):89–93
Mercer EM, Lin YC, Benner C, Jhunjhunwala S, Dutkowski J, Flores M et al (2011) Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors. Immunity 35(3):413–425
Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G et al (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448(7153):553–560
Moazed D (2009) Small RNAs in transcriptional gene silencing and genome defence. Nature 457(7228):413–420
Morris SA, Baek S, Sung MH, John S, Wiench M, Johnson TA et al (2014) Overlapping chromatin-remodeling systems collaborate genome wide at dynamic chromatin transitions. Nat Struct Mol Biol 21(1):73–81
Morrison AJ (2017) Genome maintenance functions of the INO80 chromatin remodeller. Philos Trans R Soc Lond B Biol Sci 372(1731):20160289
Morrison EA, Sanchez JC, Ronan JL, Farrell DP, Varzavand K, Johnson JK et al (2017) DNA binding drives the association of BRG1/hBRM bromodomains with nucleosomes. Nat Commun 8:16080
Muller HP, Schaffner W (1990) Transcriptional enhancers can act in trans. Trends Genet 6(9):300–304
Musselman CA, Gibson MD, Hartwick EW, North JA, Gatchalian J, Poirier MG et al (2013) Binding of PHF1 Tudor to H3K36me3 enhances nucleosome accessibility. Nat Commun 4:2969
Nagai S, Davis RE, Mattei PJ, Eagen KP, Kornberg RD (2017) Chromatin potentiates transcription. Proc Natl Acad Sci U S A 114(7):1536–1541
Ndlovu MN, Denis H, Fuks F (2011) Exposing the DNA methylome iceberg. Trends Biochem Sci 36(7):381–387
Nishioka K, Chuikov S, Sarma K, Erdjument-Bromage H, Allis CD, Tempst P et al (2002) Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev 16(4):479–489
Ocampo J, Chereji RV, Eriksson PR, Clark DJ (2016) The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo. Nucleic Acids Res 44(10):4625–4635
Ong CT, Corces VG (2011) Enhancer function: new insights into the regulation of tissue-specific gene expression. Nat Rev Genet 12(4):283–293
Ong CT, Corces VG (2012) Enhancers: emerging roles in cell fate specification. EMBO Rep 13(5):423–430
Onorati MC, Lazzaro S, Mallik M, Ingrassia AM, Carreca AP, Singh AK et al (2011) The ISWI chromatin remodeler organizes the hsromega ncRNA-containing omega speckle nuclear compartments. PLoS Genet 7(5):e1002096
Ooi SK, Qiu C, Bernstein E, Li K, Jia D, Yang Z et al (2007) DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448(7154):714–717
Parthun MR (2007) Hat1: the emerging cellular roles of a type B histone acetyltransferase. Oncogene 26(37):5319–5328
Pasini D, Malatesta M, Jung HR, Walfridsson J, Willer A, Olsson L et al (2010) Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes. Nucleic Acids Res 38(15):4958–4969
Pastor WA, Pape UJ, Huang Y, Henderson HR, Lister R, Ko M et al (2011) Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells. Nature 473(7347):394–397
Peckham HE, Thurman RE, Fu Y, Stamatoyannopoulos JA, Noble WS, Struhl K et al (2007) Nucleosome positioning signals in genomic DNA. Genome Res 17(8):1170–1177
Pekowska A, Benoukraf T, Zacarias-Cabeza J, Belhocine M, Koch F, Holota H et al (2011) H3K4 tri-methylation provides an epigenetic signature of active enhancers. EMBO J 30(20):4198–4210
Qin S, Parthun MR (2006) Recruitment of the type B histone acetyltransferase Hat1p to chromatin is linked to DNA double-strand breaks. Mol Cell Biol 26(9):3649–3658
Rada-Iglesias A, Bajpai R, Swigut T, Brugmann SA, Flynn RA, Wysocka J (2011) A unique chromatin signature uncovers early developmental enhancers in humans. Nature 470(7333):279–283
Raisner RM, Madhani HD (2006) Patterning chromatin: form and function for H2A.Z variant nucleosomes. Curr Opin Genet Dev 16(2):119–124
Ramachandran S, Zentner GE, Henikoff S (2015) Asymmetric nucleosomes flank promoters in the budding yeast genome. Genome Res 25(3):381–390
Rea S, Eisenhaber F, O’Carroll D, Strahl BD, Sun ZW, Schmid M et al (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406(6796):593–599
Reddington JP, Perricone SM, Nestor CE, Reichmann J, Youngson NA, Suzuki M et al (2013) Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes. Genome Biol 14(3):R25
Reisman D, Glaros S, Thompson EA (2009) The SWI/SNF complex and cancer. Oncogene 28(14):1653–1668
Rhee HS, Bataille AR, Zhang L, Pugh BF (2014) Subnucleosomal structures and nucleosome asymmetry across a genome. Cell 159(6):1377–1388
Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA et al (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129(7):1311–1323
Rondelet G, Dal Maso T, Willems L, Wouters J (2016) Structural basis for recognition of histone H3K36me3 nucleosome by human de novo DNA methyltransferases 3A and 3B. J Struct Biol 194(3):357–367
Rufiange A, Jacques PE, Bhat W, Robert F, Nourani A (2007) Genome-wide replication-independent histone H3 exchange occurs predominantly at promoters and implicates H3 K56 acetylation and Asf1. Mol Cell 27(3):393–405
Saha A, Wittmeyer J, Cairns BR (2006) Mechanisms for nucleosome movement by ATP-dependent chromatin remodeling complexes. Results Probl Cell Differ 41:127–148
Schneider R, Bannister AJ, Myers FA, Thorne AW, Crane-Robinson C, Kouzarides T (2004) Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat Cell Biol 6(1):73–77
Schnetz MP, Bartels CF, Shastri K, Balasubramanian D, Zentner GE, Balaji R et al (2009) Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns. Genome Res 19(4):590–601
Segal E, Fondufe-Mittendorf Y, Chen L, Thastrom A, Field Y, Moore IK et al (2006) A genomic code for nucleosome positioning. Nature 442(7104):772–778
Sen S, Block KF, Pasini A, Baylin SB, Easwaran H (2016) Genome-wide positioning of bivalent mononucleosomes. BMC Med Genomics 9(1):60
Seto E, Yoshida M (2014) Erasers of histone acetylation: the histone deacetylase enzymes. Cold Spring Harb Perspect Biol 6(4):a018713
Sharma S, Kelly TK, Jones PA (2010) Epigenetics in cancer. Carcinogenesis 31(1):27–36
Shema E, Jones D, Shoresh N, Donohue L, Ram O, Bernstein BE (2016) Single-molecule decoding of combinatorially modified nucleosomes. Science 352(6286):717–721
Shen L, Zhang Y (2013) 5-Hydroxymethylcytosine: generation, fate, and genomic distribution. Curr Opin Cell Biol 25(3):289–296
Shen W, Xu C, Huang W, Zhang J, Carlson JE, Tu X et al (2007) Solution structure of human Brg1 bromodomain and its specific binding to acetylated histone tails. Biochemistry 46(8):2100–2110
Shen Y, Matsuno Y, Fouse SD, Rao N, Root S, Xu R et al (2008) X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations. Proc Natl Acad Sci U S A 105(12):4709–4714
Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA et al (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119(7):941–953
Shi X, Hong T, Walter KL, Ewalt M, Michishita E, Hung T et al (2006) ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature 442(7098):96–99
Shogren-Knaak M, Ishii H, Sun JM, Pazin MJ, Davie JR, Peterson CL (2006) Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 311(5762):844–847
Sims RJ 3rd, Chen CF, Santos-Rosa H, Kouzarides T, Patel SS, Reinberg D (2005) Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains. J Biol Chem 280(51):41789–41792
Skulte KA, Phan L, Clark SJ, Taberlay PC (2014) Chromatin remodeler mutations in human cancers: epigenetic implications. Epigenomics 6(4):397–414
Skvortsova K, Zotenko E, Luu PL, Gould CM, Nair SS, Clark SJ et al (2017) Comprehensive evaluation of genome-wide 5-hydroxymethylcytosine profiling approaches in human DNA. Epigenetics Chromatin 10:16
Spitz F, Furlong EE (2012) Transcription factors: from enhancer binding to developmental control. Nat Rev Genet 13(9):613–626
Stadler MB, Murr R, Burger L, Ivanek R, Lienert F, Scholer A et al (2011) DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature 480(7378):490–495
Stejskal S, Stepka K, Tesarova L, Stejskal K, Matejkova M, Simara P et al (2015) Cell cycle-dependent changes in H3K56ac in human cells. Cell Cycle 14(24):3851–3863
Steunou A-L, Rossetto D, Côté J (2014) Regulating chromatin by histone acetylation. In: Workman JL, Abmayr SM (eds) Fundamentals of chromatin. Springer, New York, NY, pp 147–212
Stroud H, Feng S, Morey Kinney S, Pradhan S, Jacobsen SE (2011) 5-Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells. Genome Biol 12(6):R54
Sun XJ, Wei J, Wu XY, Hu M, Wang L, Wang HH et al (2005) Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase. J Biol Chem 280(42):35261–35271
Taberlay PC, Kelly TK, Liu CC, You JS, De Carvalho DD, Miranda TB et al (2011) Polycomb-repressed genes have permissive enhancers that initiate reprogramming. Cell 147(6):1283–1294
Taberlay PC, Statham AL, Kelly TK, Clark SJ, Jones PA (2014) Reconfiguration of nucleosome-depleted regions at distal regulatory elements accompanies DNA methylation of enhancers and insulators in cancer. Genome Res 24(9):1421–1432
Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y et al (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324(5929):930–935
Takai D, Jones PA (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci U S A 99(6):3740–3745
Tamkun JW, Deuring R, Scott MP, Kissinger M, Pattatucci AM, Kaufman TC et al (1992) brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2. Cell 68(3):561–572
Teissandier A, Bourc’his D (2017) Gene body DNA methylation conspires with H3K36me3 to preclude aberrant transcription. EMBO J 36(11):1471–1473
Tessarz P, Kouzarides T (2014) Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol 15(11):703–708
Thomson JP, Skene PJ, Selfridge J, Clouaire T, Guy J, Webb S et al (2010) CpG islands influence chromatin structure via the CpG-binding protein Cfp1. Nature 464(7291):1082–1086
Thomson JP, Hunter JM, Lempiainen H, Muller A, Terranova R, Moggs JG et al (2013) Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver. Nucleic Acids Res 41(11):5639–5654
Thurman RE, Rynes E, Humbert R, Vierstra J, Maurano MT, Haugen E et al (2012) The accessible chromatin landscape of the human genome. Nature 489(7414):75–82
Tjeertes JV, Miller KM, Jackson SP (2009) Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells. EMBO J 28(13):1878–1889
Tolstorukov MY, Sansam CG, Lu P, Koellhoffer EC, Helming KC, Alver BH et al (2013) Swi/Snf chromatin remodeling/tumor suppressor complex establishes nucleosome occupancy at target promoters. Proc Natl Acad Sci U S A 110(25):10165–10170
Trojer P, Li G, Sims RJ 3rd, Vaquero A, Kalakonda N, Boccuni P et al (2007) L3MBTL1, a histone-methylation-dependent chromatin lock. Cell 129(5):915–928
Tropberger P, Pott S, Keller C, Kamieniarz-Gdula K, Caron M, Richter F et al (2013) Regulation of transcription through acetylation of H3K122 on the lateral surface of the histone octamer. Cell 152(4):859–872
Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F et al (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329(5992):689–693
Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P et al (2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439(7078):811–816
Valdes-Mora F, Song JZ, Statham AL, Strbenac D, Robinson MD, Nair SS et al (2012) Acetylation of H2A.Z is a key epigenetic modification associated with gene deregulation and epigenetic remodeling in cancer. Genome Res 22(2):307–321
Valdes-Mora F, Gould CM, Colino-Sanguino Y, Qu W, Song JZ, Taylor KM et al (2017) Acetylated histone variant H2A.Z is involved in the activation of neo-enhancers in prostate cancer. Nat Commun 8(1):1346
Valouev A, Johnson SM, Boyd SD, Smith CL, Fire AZ, Sidow A (2011) Determinants of nucleosome organization in primary human cells. Nature 474(7352):516–520
Vempati RK, Jayani RS, Notani D, Sengupta A, Galande S, Haldar D (2010) p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage response in mammals. J Biol Chem 285(37):28553–28564
Venkatesh S, Workman JL (2015) Histone exchange, chromatin structure and the regulation of transcription. Nat Rev Mol Cell Biol 16(3):178–189
Verma N, Pan H, Dore LC, Shukla A, Li QV, Pelham-Webb B et al (2018) TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells. Nat Genet 50(1):83–95
Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C et al (2006) The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439(7078):871–874
Visel A, Blow MJ, Li Z, Zhang T, Akiyama JA, Holt A et al (2009) ChIP-seq accurately predicts tissue-specific activity of enhancers. Nature 457(7231):854–858
Voigt P, LeRoy G, Drury WJ 3rd, Zee BM, Son J, Beck DB et al (2012) Asymmetrically modified nucleosomes. Cell 151(1):181–193
Voigt P, Tee WW, Reinberg D (2013) A double take on bivalent promoters. Genes Dev 27(12):1318–1338
Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S et al (2008) Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40(7):897–903
Wang J, Qin S, Li F, Li S, Zhang W, Peng J et al (2014) Crystal structure of human BS69 Bromo-ZnF-PWWP reveals its role in H3K36me3 nucleosome binding. Cell Res 24(7):890–893
Wang DY, An SH, Liu L, Bai SS, Wu KX, Zhu R et al (2016) Hepatitis B virus X protein influences enrichment profiles of H3K9me3 on promoter regions in human hepatoma cell lines. Oncotarget 7(51):84883–84892
Wani AH, Boettiger AN, Schorderet P, Ergun A, Munger C, Sadreyev RI et al (2016) Chromatin topology is coupled to Polycomb group protein subnuclear organization. Nat Commun 7:10291
Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z et al (2006) Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell 125(3):467–481
Widschwendter M, Fiegl H, Egle D, Mueller-Holzner E, Spizzo G, Marth C et al (2007) Epigenetic stem cell signature in cancer. Nat Genet 39(2):157–158
Wilson BG, Wang X, Shen X, McKenna ES, Lemieux ME, Cho YJ et al (2010) Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell 18(4):316–328
Wurtele H, Kaiser GS, Bacal J, St-Hilaire E, Lee EH, Tsao S et al (2012) Histone H3 lysine 56 acetylation and the response to DNA replication fork damage. Mol Cell Biol 32(1):154–172
Wysocka J, Swigut T, Xiao H, Milne TA, Kwon SY, Landry J et al (2006) A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling. Nature 442(7098):86–90
Xhemalce B, Dawson MA, Bannister AJ (2011) Histone modifications. Reviews in cell biology and molecular medicine. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Xia RH, Wang Z, Zhang CY, Hu YH, Zhou RR, Wang LZ et al (2015) Low expression of endothelin receptor B (EDNRB) is related to H3K9me3 binding with the EDNRB promoter region and is associated with the clinical T tumor stage in salivary adenoid cystic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 120(2):258–268
Xiao B, Jing C, Wilson JR, Walker PA, Vasisht N, Kelly G et al (2003) Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature 421(6923):652–656
Xu F, Zhang K, Grunstein M (2005) Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell 121(3):375–385
Yang XJ, Seto E (2008) The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol 9(3):206–218
Yang X, Noushmehr H, Han H, Andreu-Vieyra C, Liang G, Jones PA (2012) Gene reactivation by 5-aza-2’-deoxycytidine-induced demethylation requires SRCAP-mediated H2A.Z insertion to establish nucleosome depleted regions. PLoS Genet 8(3):e1002604
You JS, Jones PA (2012) Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 22(1):9–20
You JS, Kelly TK, De Carvalho DD, Taberlay PC, Liang G, Jones PA (2011) OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genes. Proc Natl Acad Sci U S A 108(35):14497–14502
Zegerman P, Canas B, Pappin D, Kouzarides T (2002) Histone H3 lysine 4 methylation disrupts binding of nucleosome remodeling and deacetylase (NuRD) repressor complex. J Biol Chem 277(14):11621–11624
Zentner GE, Henikoff S (2013) Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol 20(3):259–266
Zentner GE, Tesar PJ, Scacheri PC (2011) Epigenetic signatures distinguish multiple classes of enhancers with distinct cellular functions. Genome Res 21(8):1273–1283
Zentner GE, Tsukiyama T, Henikoff S (2013) ISWI and CHD chromatin remodelers bind promoters but act in gene bodies. PLoS Genet 9(2):e1003317
Zhang X, Yang Z, Khan SI, Horton JR, Tamaru H, Selker EU et al (2003) Structural basis for the product specificity of histone lysine methyltransferases. Mol Cell 12(1):177–185
Zhang W, Prakash C, Sum C, Gong Y, Li Y, Kwok JJ et al (2012) Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem 287(51):43137–43155
Zheng H, Huang B, Zhang B, Xiang Y, Du Z, Xu Q et al (2016) Resetting epigenetic memory by reprogramming of histone modifications in mammals. Mol Cell 63(6):1066–1079
Zhou Y, Zheng L, Li F, Wan M, Fan Y, Zhou X et al (2018) Bivalent histone codes on WNT5A during odontogenic differentiation. J Dent Res 97:99–107
Zhu K, Lei PJ, Ju LG, Wang X, Huang K, Yang B et al (2017) SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing. Nucleic Acids Res 45(1):92–105
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Giles, K.A., Taberlay, P.C. (2019). The Role of Nucleosomes in Epigenetic Gene Regulation. In: Hesson, L., Pritchard, A. (eds) Clinical Epigenetics. Springer, Singapore. https://doi.org/10.1007/978-981-13-8958-0_4
Download citation
DOI: https://doi.org/10.1007/978-981-13-8958-0_4
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-8957-3
Online ISBN: 978-981-13-8958-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)