Cellular and Molecular Life Sciences

, Volume 72, Issue 13, pp 2491–2507 | Cite as

Structure and function insights into the NuRD chromatin remodeling complex

  • Morgan P. Torchy
  • Ali Hamiche
  • Bruno P. Klaholz
Review

Abstract

Transcription regulation through chromatin compaction and decompaction is regulated through various chromatin-remodeling complexes such as nucleosome remodeling and histone deacetylation (NuRD) complex. NuRD is a 1 MDa multi-subunit protein complex which comprises many different subunits, among which histone deacetylases HDAC1/2, ATP-dependent remodeling enzymes CHD3/4, histone chaperones RbAp46/48, CpG-binding proteins MBD2/3, the GATAD2a (p66α) and/or GATAD2b (p66β) and specific DNA-binding proteins MTA1/2/3. Here, we review the currently known crystal and NMR structures of these subunits, the functional data and their relevance for biomedical research considering the implication of NuRD subunits in cancer and various other diseases. The complexity of this macromolecular assembly, and its poorly understood mode of interaction with the nucleosome, the repeating unit of chromatin, illustrate that this complex is a major challenge for structure–function relationship studies which will be tackled best by an integrated biology approach.

Keywords

NuRD Remodeling Deacetylase Chromatin Nucleosome Structural biology 

Notes

Acknowledgments

This work was supported by the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale pour la Recherche (ANR), the Association pour la Recherche sur le Cancer (ARC), the Centre Nationale pour la Recherche Scientifique (CNRS), and by the French Infrastructure for Integrated Structural Biology (FRISBI) ANR-10-INSB-05-01, and Instruct as part of the European Strategy Forum on Research Infrastructures (ESFRI). We thank the referees for nice suggestions.

Conflict of interest

The authors declare no competing financial interests.

References

  1. 1.
    Waddington CH (2012) The epigenotype. Int J Epidemiol 41:10–13PubMedGoogle Scholar
  2. 2.
    Wade PA, Jones PL, Vermaak D, Wolffe AP (1998) A multiple subunit Mi-2 histone deacetylase from Xenopus laevis cofractionates with an associated Snf2 superfamily ATPase. Curr Biol 8:843–846PubMedGoogle Scholar
  3. 3.
    Xue Y et al (1998) NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell 2:851–861PubMedGoogle Scholar
  4. 4.
    Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL (1998) Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex. Nature 395:917–921PubMedGoogle Scholar
  5. 5.
    Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D (1998) The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 95:279–289PubMedGoogle Scholar
  6. 6.
    Allen HF, Wade PA, Kutateladze TG (2013) The NuRD architecture. Cell Mol Life Sci 70:3513–3524PubMedCentralPubMedGoogle Scholar
  7. 7.
    Auger A et al (2008) Eaf1 is the platform for NuA4 molecular assembly that evolutionarily links chromatin acetylation to ATP-dependent exchange of histone H2A variants. Mol Cell Biol 28:2257–2270PubMedCentralPubMedGoogle Scholar
  8. 8.
    Doyon Y, Cote J (2004) The highly conserved and multifunctional NuA4 HAT complex. Curr Opin Genet Dev 14:147–154PubMedGoogle Scholar
  9. 9.
    Verreault A, Kaufman PD, Kobayashi R, Stillman B (1998) Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase. Curr Biol 8:96–108PubMedGoogle Scholar
  10. 10.
    Le Guezennec X et al (2006) MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties. Mol Cell Biol 26:843–851PubMedCentralPubMedGoogle Scholar
  11. 11.
    Fujita N et al (2003) MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell 113:207–219PubMedGoogle Scholar
  12. 12.
    Smits AH, Jansen PW, Poser I, Hyman AA, Vermeulen M (2013) Stoichiometry of chromatin-associated protein complexes revealed by label-free quantitative mass spectrometry-based proteomics. Nucleic Acids Res 41:e28PubMedCentralPubMedGoogle Scholar
  13. 13.
    Millard CJ et al (2013) Class I HDACs share a common mechanism of regulation by inositol phosphates. Mol Cell 51:57–67PubMedCentralPubMedGoogle Scholar
  14. 14.
    Wang Y et al (2009) LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer. Cell 138:660–672PubMedGoogle Scholar
  15. 15.
    Georgopoulos K, Winandy S, Avitahl N (1997) The role of the Ikaros gene in lymphocyte development and homeostasis. Annu Rev Immunol 15:155–176PubMedGoogle Scholar
  16. 16.
    Kim J et al (1999) Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity 10:345–355PubMedGoogle Scholar
  17. 17.
    Sridharan R, Smale ST (2007) Predominant interaction of both Ikaros and Helios with the NuRD complex in immature thymocytes. J Biol Chem 282:30227–30238PubMedGoogle Scholar
  18. 18.
    Miles RR, Crockett DK, Lim MS, Elenitoba-Johnson KS (2005) Analysis of BCL6-interacting proteins by tandem mass spectrometry. Mol Cell Proteomics 4:1898–1909PubMedGoogle Scholar
  19. 19.
    Fujita N et al (2004) MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation. Cell 119:75–86PubMedGoogle Scholar
  20. 20.
    Okada M et al (2008) Switching of chromatin-remodelling complexes for oestrogen receptor-alpha. EMBO Rep 9:563–568PubMedCentralPubMedGoogle Scholar
  21. 21.
    Mazumdar A et al (2001) Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol 3:30–37PubMedGoogle Scholar
  22. 22.
    Cui Y et al (2006) Metastasis-associated protein 2 is a repressor of estrogen receptor alpha whose overexpression leads to estrogen-independent growth of human breast cancer cells. Mol Endocrinol 20:2020–2035PubMedGoogle Scholar
  23. 23.
    Kaji K et al (2006) The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nat Cell Biol 8:285–292PubMedGoogle Scholar
  24. 24.
    Kaji K, Nichols J, Hendrich B (2007) Mbd3, a component of the NuRD co-repressor complex, is required for development of pluripotent cells. Development 134:1123–1132PubMedGoogle Scholar
  25. 25.
    Hill CL et al (2001) Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet 357:96–100PubMedGoogle Scholar
  26. 26.
    Seelig HP et al (1995) The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation. Arthritis Rheum 38:1389–1399PubMedGoogle Scholar
  27. 27.
    Ge Q, Nilasena DS, O’Brien CA, Frank MB, Targoff IN (1995) Molecular analysis of a major antigenic region of the 240-kD protein of Mi-2 autoantigen. J Clin Invest 96:1730–1737PubMedCentralPubMedGoogle Scholar
  28. 28.
    Callen JP, Wortmann RL (2006) Dermatomyositis. Clin Dermatol 24:363–373PubMedGoogle Scholar
  29. 29.
    Woodage T, Basrai MA, Baxevanis AD, Hieter P, Collins FS (1997) Characterization of the CHD family of proteins. Proc Natl Acad Sci USA 94:11472–11477PubMedCentralPubMedGoogle Scholar
  30. 30.
    Brehm A et al (2000) dMi-2 and ISWI chromatin remodelling factors have distinct nucleosome binding and mobilization properties. EMBO J 19:4332–4341PubMedCentralPubMedGoogle Scholar
  31. 31.
    Wang HB, Zhang Y (2001) Mi2, an auto-antigen for dermatomyositis, is an ATP-dependent nucleosome remodeling factor. Nucleic Acids Res 29:2517–2521PubMedCentralPubMedGoogle Scholar
  32. 32.
    Kwan AH et al (2003) Engineering a protein scaffold from a PHD finger. Structure 11:803–813PubMedGoogle Scholar
  33. 33.
    Mansfield RE et al (2011) Plant homeodomain (PHD) fingers of CHD4 are histone H3-binding modules with preference for unmodified H3K4 and methylated H3K9. J Biol Chem 286:11779–11791PubMedCentralPubMedGoogle Scholar
  34. 34.
    Musselman CA et al (2012) Bivalent recognition of nucleosomes by the tandem PHD fingers of the CHD4 ATPase is required for CHD4-mediated repression. Proc Natl Acad Sci USA 109:787–792PubMedCentralPubMedGoogle Scholar
  35. 35.
    Musselman CA et al (2009) Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications. Biochem J 423:179–187PubMedCentralPubMedGoogle Scholar
  36. 36.
    Morra R, Lee BM, Shaw H, Tuma R, Mancini EJ (2012) Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4. FEBS Lett 586:2513–2521PubMedCentralPubMedGoogle Scholar
  37. 37.
    Watson AA et al (2012) The PHD and chromo domains regulate the ATPase activity of the human chromatin remodeler CHD4. J Mol Biol 422:3–17PubMedCentralPubMedGoogle Scholar
  38. 38.
    Goodarzi AA, Kurka T, Jeggo PA (2011) KAP-1 phosphorylation regulates CHD3 nucleosome remodeling during the DNA double-strand break response. Nat Struct Mol Biol 18:831–839PubMedGoogle Scholar
  39. 39.
    Ivanov AV et al (2007) PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing. Mol Cell 28:823–837PubMedCentralPubMedGoogle Scholar
  40. 40.
    Lee DH et al (2012) Phosphoproteomic analysis reveals that PP4 dephosphorylates KAP-1 impacting the DNA damage response. EMBO J 31:2403–2415PubMedCentralPubMedGoogle Scholar
  41. 41.
    von Zelewsky T et al (2000) The C. elegans Mi-2 chromatin-remodelling proteins function in vulval cell fate determination. Development 127:5277–5284Google Scholar
  42. 42.
    Fukaki H, Taniguchi N, Tasaka M (2006) PICKLE is required for SOLITARY-ROOT/IAA14-mediated repression of ARF7 and ARF19 activity during Arabidopsis lateral root initiation. Plant J 48:380–389PubMedGoogle Scholar
  43. 43.
    Itazaki H et al (1990) Isolation and structural elucidation of new cyclotetrapeptides, trapoxin-A and Trapoxin-B, having detransformation activities as antitumor agents. J Antibiot 43:1524–1532PubMedGoogle Scholar
  44. 44.
    Kijima M, Yoshida M, Sugita K, Horinouchi S, Beppu T (1993) Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase. J Biol Chem 268:22429–22435PubMedGoogle Scholar
  45. 45.
    Taunton J, Hassig CA, Schreiber SL (1996) A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272:408–411PubMedGoogle Scholar
  46. 46.
    Dovey OM et al (2013) Histone deacetylase 1 and 2 are essential for normal T-cell development and genomic stability in mice. Blood 121:1335–1344PubMedGoogle Scholar
  47. 47.
    Sun JM, Chen HY, Davie JR (2007) Differential distribution of unmodified and phosphorylated histone deacetylase 2 in chromatin. J Biol Chem 282:33227–33236PubMedGoogle Scholar
  48. 48.
    Pflum MK, Tong JK, Lane WS, Schreiber SL (2001) Histone deacetylase 1 phosphorylation promotes enzymatic activity and complex formation. J Biol Chem 276:47733–47741PubMedGoogle Scholar
  49. 49.
    Segre CV, Chiocca S (2011) Regulating the regulators: the post-translational code of class I HDAC1 and HDAC2. J Biomed Biotechnol 2011:690848PubMedCentralPubMedGoogle Scholar
  50. 50.
    Somoza JR et al (2004) Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure 12:1325–1334PubMedGoogle Scholar
  51. 51.
    Vannini A et al (2004) Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proc Natl Acad Sci USA 101:15064–15069PubMedCentralPubMedGoogle Scholar
  52. 52.
    Bressi JC et al (2010) Exploration of the HDAC2 foot pocket: synthesis and SAR of substituted N-(2-aminophenyl)benzamides. Bioorg Med Chem Lett 20:3142–3145PubMedGoogle Scholar
  53. 53.
    Lauffer BE et al (2013) Histone deacetylase (HDAC) inhibitor kinetic rate constants correlate with cellular histone acetylation but not transcription and cell viability. J Biol Chem 288:26926–26943PubMedCentralPubMedGoogle Scholar
  54. 54.
    Aguilera C et al (2011) c-Jun N-terminal phosphorylation antagonises recruitment of the Mbd3/NuRD repressor complex. Nature 469:231–235PubMedGoogle Scholar
  55. 55.
    Montgomery RL et al (2007) Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. Genes Dev 21:1790–1802PubMedCentralPubMedGoogle Scholar
  56. 56.
    Yamaguchi J et al (2010) Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma. Cancer Sci 101:355–362PubMedGoogle Scholar
  57. 57.
    Zupkovitz G et al (2006) Negative and positive regulation of gene expression by mouse histone deacetylase 1. Mol Cell Biol 26:7913–7928PubMedCentralPubMedGoogle Scholar
  58. 58.
    Wang Z et al (2009) Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes. Cell 138:1019–1031PubMedCentralPubMedGoogle Scholar
  59. 59.
    Kidder BL, Palmer S (2012) HDAC1 regulates pluripotency and lineage specific transcriptional networks in embryonic and trophoblast stem cells. Nucleic Acids Res 40:2925–2939PubMedCentralPubMedGoogle Scholar
  60. 60.
    Kurdistani SK, Robyr D, Tavazoie S, Grunstein M (2002) Genome-wide binding map of the histone deacetylase Rpd3 in yeast. Nat Genet 31:248–254PubMedGoogle Scholar
  61. 61.
    Lagger G et al (2002) Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. EMBO J 21:2672–2681PubMedCentralPubMedGoogle Scholar
  62. 62.
    Senese S et al (2007) Role for histone deacetylase 1 in human tumor cell proliferation. Mol Cell Biol 27:4784–4795PubMedCentralPubMedGoogle Scholar
  63. 63.
    Wilting RH et al (2010) Overlapping functions of Hdac1 and Hdac2 in cell cycle regulation and haematopoiesis. EMBO J 29:2586–2597PubMedCentralPubMedGoogle Scholar
  64. 64.
    Zupkovitz G et al (2010) The cyclin-dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation. Mol Cell Biol 30:1171–1181PubMedCentralPubMedGoogle Scholar
  65. 65.
    Marks PA, Xu WS (2009) Histone deacetylase inhibitors: Potential in cancer therapy. J Cell Biochem 107:600–608PubMedCentralPubMedGoogle Scholar
  66. 66.
    Rosato RR, Almenara JA, Grant S (2003) The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1. Cancer Res 63:3637–3645PubMedGoogle Scholar
  67. 67.
    Dovey OM, Foster CT, Cowley SM (2010) Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation. Proc Natl Acad Sci USA 107:8242–8247PubMedCentralPubMedGoogle Scholar
  68. 68.
    Dovey OM, Foster CT, Cowley SM (2010) Emphasizing the positive: a role for histone deacetylases in transcriptional activation. Cell Cycle 9:2700–2701PubMedGoogle Scholar
  69. 69.
    LeBoeuf M et al (2010) Hdac1 and Hdac2 act redundantly to control p63 and p53 functions in epidermal progenitor cells. Dev Cell 19:807–818PubMedCentralPubMedGoogle Scholar
  70. 70.
    Ma P, Pan H, Montgomery RL, Olson EN, Schultz RM (2012) Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development. Proc Natl Acad Sci USA 109:E481–E489PubMedCentralPubMedGoogle Scholar
  71. 71.
    Pencil SD, Toh Y, Nicolson GL (1993) Candidate metastasis-associated genes of the rat 13762NF mammary adenocarcinoma. Breast Cancer Res Treat 25:165–174PubMedGoogle Scholar
  72. 72.
    Bowen NJ, Fujita N, Kajita M, Wade PA (2004) Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta 1677:52–57PubMedGoogle Scholar
  73. 73.
    Yaguchi M et al (2005) Identification and characterization of the variants of metastasis-associated protein 1 generated following alternative splicing. Biochim Biophys Acta 1732:8–14PubMedGoogle Scholar
  74. 74.
    Boyer LA et al (2002) Essential role for the SANT domain in the functioning of multiple chromatin remodeling enzymes. Mol Cell 10:935–942PubMedGoogle Scholar
  75. 75.
    Yu J, Li Y, Ishizuka T, Guenther MG, Lazar MA (2003) A SANT motif in the SMRT corepressor interprets the histone code and promotes histone deacetylation. EMBO J 22:3403–3410PubMedCentralPubMedGoogle Scholar
  76. 76.
    Watson PJ, Fairall L, Santos GM, Schwabe JW (2012) Structure of HDAC3 bound to co-repressor and inositol tetraphosphate. Nature 481:335–340PubMedCentralPubMedGoogle Scholar
  77. 77.
    Millard CJ, Fairall L, Schwabe, JW (2014) Towards an understanding of the structure and function of MTA1. Cancer Metastasis Rev 33(4):857–867PubMedCentralPubMedGoogle Scholar
  78. 78.
    Chambers AL, Pearl LH, Oliver AW, Downs JA (2013) The BAH domain of Rsc2 is a histone H3 binding domain. Nucleic Acids Res 41:9168–9182PubMedCentralPubMedGoogle Scholar
  79. 79.
    Kuo AJ et al (2012) The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier–Gorlin syndrome. Nature 484:115–119PubMedCentralPubMedGoogle Scholar
  80. 80.
    Merika M, Orkin SH (1993) DNA-binding specificity of GATA family transcription factors. Mol Cell Biol 13:3999–4010PubMedCentralPubMedGoogle Scholar
  81. 81.
    Zhang XY et al (2005) Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein. Proc Natl Acad Sci USA 102:13968–13973PubMedCentralPubMedGoogle Scholar
  82. 82.
    Yoo YG, Kong G, Lee MO (2006) Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. EMBO J 25:1231–1241PubMedCentralPubMedGoogle Scholar
  83. 83.
    Kumar R (2003) Another tie that binds the MTA family to breast cancer. Cell 113:142–143PubMedGoogle Scholar
  84. 84.
    Manavathi B, Kumar R (2007) Metastasis tumor antigens, an emerging family of multifaceted master coregulators. J Biol Chem 282:1529–1533PubMedGoogle Scholar
  85. 85.
    Kumar R et al (2002) A naturally occurring MTA1 variant sequesters oestrogen receptor-alpha in the cytoplasm. Nature 418:654–657PubMedGoogle Scholar
  86. 86.
    Zhang H, Singh RR, Talukder AH, Kumar R (2006) Metastatic tumor antigen 3 is a direct corepressor of the Wnt4 pathway. Genes Dev 20:2943–2948PubMedCentralPubMedGoogle Scholar
  87. 87.
    Kleene R, Classen B, Zdzieblo J, Schrader M (2000) SH3 binding sites of ZG29p mediate an interaction with amylase and are involved in condensation-sorting in the exocrine rat pancreas. Biochemistry 39:9893–9900PubMedGoogle Scholar
  88. 88.
    Lewis JD et al (1992) Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69:905–914PubMedGoogle Scholar
  89. 89.
    Meehan RR, Lewis JD, McKay S, Kleiner EL, Bird AP (1989) Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs. Cell 58:499–507PubMedGoogle Scholar
  90. 90.
    Amir RE et al (1999) Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23:185–188PubMedGoogle Scholar
  91. 91.
    Nagarajan RP, Hogart AR, Gwye Y, Martin MR, LaSalle JM (2006) Reduced MeCP2 expression is frequent in autism frontal cortex and correlates with aberrant MECP2 promoter methylation. Epigenetics 1:e1–11PubMedCentralPubMedGoogle Scholar
  92. 92.
    Nan X, Meehan RR, Bird A (1993) Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2. Nucleic Acids Res 21:4886–4892PubMedCentralPubMedGoogle Scholar
  93. 93.
    Nan X et al (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386–389PubMedGoogle Scholar
  94. 94.
    Hendrich B, Bird A (1998) Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol 18:6538–6547PubMedCentralPubMedGoogle Scholar
  95. 95.
    Lyko F, Ramsahoye BH, Jaenisch R (2000) DNA methylation in Drosophila melanogaster. Nature 408:538–540PubMedGoogle Scholar
  96. 96.
    Marhold J, Kramer K, Kremmer E, Lyko F (2004) The Drosophila MBD2/3 protein mediates interactions between the MI-2 chromatin complex and CpT/A-methylated DNA. Development 131:6033–6039PubMedGoogle Scholar
  97. 97.
    Ng HH et al (1999) MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat Genet 23:58–61PubMedGoogle Scholar
  98. 98.
    Fraga MF et al (2003) The affinity of different MBD proteins for a specific methylated locus depends on their intrinsic binding properties. Nucleic Acids Res 31:1765–1774PubMedCentralPubMedGoogle Scholar
  99. 99.
    Hendrich B, Tweedie S (2003) The methyl-CpG binding domain and the evolving role of DNA methylation in animals. Trends Genet 19:269–277PubMedGoogle Scholar
  100. 100.
    Saito M, Ishikawa F (2002) The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2. J Biol Chem 277:35434–35439PubMedGoogle Scholar
  101. 101.
    Zhang Y et al (1999) Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev 13:1924–1935PubMedCentralPubMedGoogle Scholar
  102. 102.
    Wade PA et al (1999) Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nat Genet 23:62–66PubMedGoogle Scholar
  103. 103.
    Feng Q, Zhang Y (2001) The MeCP1 complex represses transcription through preferential binding, remodeling, and deacetylating methylated nucleosomes. Genes Dev 15:827–832PubMedCentralPubMedGoogle Scholar
  104. 104.
    Hendrich B, Guy J, Ramsahoye B, Wilson VA, Bird A (2001) Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development. Genes Dev 15:710–723PubMedCentralPubMedGoogle Scholar
  105. 105.
    Yildirim O et al (2011) Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells. Cell 147:1498–1510PubMedCentralPubMedGoogle Scholar
  106. 106.
    Hashimoto H et al (2012) Recognition and potential mechanisms for replication and erasure of cytosine hydroxymethylation. Nucleic Acids Res 40:4841–4849PubMedCentralPubMedGoogle Scholar
  107. 107.
    Baubec T, Ivanek R, Lienert F, Schubeler D (2013) Methylation-dependent and -independent genomic targeting principles of the MBD protein family. Cell 153:480–492PubMedGoogle Scholar
  108. 108.
    Shimbo T et al (2013) MBD3 localizes at promoters, gene bodies and enhancers of active genes. PLoS Genet 9:e1004028PubMedCentralPubMedGoogle Scholar
  109. 109.
    Cramer JM et al (2014) Probing the dynamic distribution of bound states for methylcytosine-binding domains on DNA. J Biol Chem 289:1294–1302PubMedCentralPubMedGoogle Scholar
  110. 110.
    Ho KL et al (2008) MeCP2 binding to DNA depends upon hydration at methyl-CpG. Mol Cell 29:525–531PubMedGoogle Scholar
  111. 111.
    Ohki I et al (2001) Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA. Cell 105:487–497PubMedGoogle Scholar
  112. 112.
    Ohki I, Shimotake N, Fujita N, Nakao M, Shirakawa M (1999) Solution structure of the methyl-CpG-binding domain of the methylation-dependent transcriptional repressor MBD1. EMBO J 18:6653–6661PubMedCentralPubMedGoogle Scholar
  113. 113.
    Otani J et al (2013) Structural basis of the versatile DNA recognition ability of the methyl-CpG binding domain of methyl-CpG binding domain protein 4. J Biol Chem 288:6351–6362PubMedCentralPubMedGoogle Scholar
  114. 114.
    Scarsdale JN, Webb HD, Ginder GD, Williams DC Jr (2011) Solution structure and dynamic analysis of chicken MBD2 methyl binding domain bound to a target-methylated DNA sequence. Nucleic Acids Res 39:6741–6752PubMedCentralPubMedGoogle Scholar
  115. 115.
    Wakefield RI et al (1999) The solution structure of the domain from MeCP2 that binds to methylated DNA. J Mol Biol 291:1055–1065PubMedGoogle Scholar
  116. 116.
    Gnanapragasam MN et al (2011) p66Alpha-MBD2 coiled-coil interaction and recruitment of Mi-2 are critical for globin gene silencing by the MBD2-NuRD complex. Proc Natl Acad Sci USA 108:7487–7492PubMedCentralPubMedGoogle Scholar
  117. 117.
    Huntriss J et al (2004) Expression of mRNAs for DNA methyltransferases and methyl-CpG-binding proteins in the human female germ line, preimplantation embryos, and embryonic stem cells. Mol Reprod Dev 67:323–336PubMedGoogle Scholar
  118. 118.
    Kantor B, Makedonski K, Shemer R, Razin A (2003) Expression and localization of components of the histone deacetylases multiprotein repressory complexes in the mouse preimplantation embryo. Gene Expr Patterns 3:697–702PubMedGoogle Scholar
  119. 119.
    Cassel S, Revel MO, Kelche C, Zwiller J (2004) Expression of the methyl-CpG-binding protein MeCP2 in rat brain. An ontogenetic study. Neurobiol Dis 15:206–211PubMedGoogle Scholar
  120. 120.
    Urdinguio RG et al (2008) Mecp2-null mice provide new neuronal targets for Rett syndrome. PLoS ONE 3:e3669PubMedCentralPubMedGoogle Scholar
  121. 121.
    Auriol E, Billard LM, Magdinier F, Dante R (2005) Specific binding of the methyl binding domain protein 2 at the BRCA1-NBR2 locus. Nucleic Acids Res 33:4243–4254PubMedCentralPubMedGoogle Scholar
  122. 122.
    Rais Y et al (2013) Deterministic direct reprogramming of somatic cells to pluripotency. Nature 502:65–70PubMedGoogle Scholar
  123. 123.
    Dos Santos RL et al (2014) MBD3/NuRD facilitates induction of pluripotency in a context-dependent manner. Cell Stem Cell 15:102–110PubMedCentralPubMedGoogle Scholar
  124. 124.
    Cukier HN et al (2010) Novel variants identified in methyl-CpG-binding domain genes in autistic individuals. Neurogenetics 11:291–303PubMedCentralPubMedGoogle Scholar
  125. 125.
    Nicolas E et al (2000) RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein. J Biol Chem 275:9797–9804PubMedGoogle Scholar
  126. 126.
    Qian YW, Lee EY (1995) Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast. J Biol Chem 270:25507–25513PubMedGoogle Scholar
  127. 127.
    Qian YW et al (1993) A retinoblastoma-binding protein related to a negative regulator of Ras in yeast. Nature 364:648–652PubMedGoogle Scholar
  128. 128.
    Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D (1997) Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex. Cell 89:357–364PubMedGoogle Scholar
  129. 129.
    Knoepfler PS, Eisenman RN (1999) Sin meets NuRD and other tails of repression. Cell 99:447–450PubMedGoogle Scholar
  130. 130.
    Ahringer J (2000) NuRD and SIN3 histone deacetylase complexes in development. Trends Genet 16:351–356PubMedGoogle Scholar
  131. 131.
    Parthun MR (2007) Hat1: the emerging cellular roles of a type B histone acetyltransferase. Oncogene 26:5319–5328PubMedGoogle Scholar
  132. 132.
    Benson LJ et al (2007) Properties of the type B histone acetyltransferase Hat 1: H4 tail interaction, site preference, and involvement in DNA repair. J Biol Chem 282:836–842PubMedGoogle Scholar
  133. 133.
    Hoek M, Stillman B (2003) Chromatin assembly factor 1 is essential and couples chromatin assembly to DNA replication in vivo. Proc Natl Acad Sci USA 100:12183–12188PubMedCentralPubMedGoogle Scholar
  134. 134.
    Korenjak M et al (2004) Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes. Cell 119:181–193PubMedGoogle Scholar
  135. 135.
    Kuzmichev A, Jenuwein T, Tempst P, Reinberg D (2004) Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3. Mol Cell 14:183–193PubMedGoogle Scholar
  136. 136.
    Martinez-Balbas MA, Tsukiyama T, Gdula D, Wu C (1998) Drosophila NURF-55, a WD repeat protein involved in histone metabolism. Proc Natl Acad Sci USA 95:132–137PubMedCentralPubMedGoogle Scholar
  137. 137.
    Murzina NV et al (2008) Structural basis for the recognition of histone H4 by the histone-chaperone RbAp46. Structure 16:1077–1085PubMedCentralPubMedGoogle Scholar
  138. 138.
    Xu C, Min J (2011) Structure and function of WD40 domain proteins. Protein Cell 2:202–214PubMedGoogle Scholar
  139. 139.
    Lejon S et al (2011) Insights into association of the NuRD complex with FOG-1 from the crystal structure of an RbAp48.FOG-1 complex. J Biol Chem 286:1196–1203PubMedCentralPubMedGoogle Scholar
  140. 140.
    Alqarni SS et al (2014) Insight into the architecture of the NuRD complex: Structure of the RbAp48-MTA1 sub-complex. J Biol Chem 289(32):21844–21855PubMedCentralPubMedGoogle Scholar
  141. 141.
    Zhang W et al (2013) Structural plasticity of histones H3–H4 facilitates their allosteric exchange between RbAp48 and ASF1. Nat Struct Mol Biol 20:29–35PubMedCentralPubMedGoogle Scholar
  142. 142.
    Guan LS, Li GC, Chen CC, Liu LQ, Wang ZY (2001) Rb-associated protein 46 (RbAp46) suppresses the tumorigenicity of adenovirus-transformed human embryonic kidney 293 cells. Int J Cancer 93:333–338PubMedGoogle Scholar
  143. 143.
    Thakur A et al (2007) Aberrant expression of X-linked genes RbAp46, Rsk4, and Cldn2 in breast cancer. Mol Cancer Res 5:171–181PubMedGoogle Scholar
  144. 144.
    Zhang TF, Yu SQ, Deuel TF, Wang ZY (2003) Constitutive expression of Rb associated protein 46 (RbAp46) reverts transformed phenotypes of breast cancer cells. Anticancer Res 23:3735–3740PubMedGoogle Scholar
  145. 145.
    Creekmore AL et al (2008) The role of retinoblastoma-associated proteins 46 and 48 in estrogen receptor alpha mediated gene expression. Mol Cell Endocrinol 291:79–86PubMedCentralPubMedGoogle Scholar
  146. 146.
    Kong L et al (2007) RbAp48 is a critical mediator controlling the transforming activity of human papillomavirus type 16 in cervical cancer. J Biol Chem 282:26381–26391PubMedGoogle Scholar
  147. 147.
    Ginger MR, Gonzalez-Rimbau MF, Gay JP, Rosen JM (2001) Persistent changes in gene expression induced by estrogen and progesterone in the rat mammary gland. Mol Endocrinol 15:1993–2009PubMedGoogle Scholar
  148. 148.
    Zheng L et al (2013) Radiation-inducible protein RbAp48 contributes to radiosensitivity of cervical cancer cells. Gynecol Oncol 130:601–608PubMedGoogle Scholar
  149. 149.
    Pavlopoulos E et al (2013) Molecular mechanism for age-related memory loss: the histone-binding protein RbAp48. Sci Transl Med 5:200ra115PubMedGoogle Scholar
  150. 150.
    Feng Q et al (2002) Identification and functional characterization of the p66/p68 components of the MeCP1 complex. Mol Cell Biol 22:536–546PubMedCentralPubMedGoogle Scholar
  151. 151.
    Brackertz M, Boeke J, Zhang R, Renkawitz R (2002) Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3. J Biol Chem 277:40958–40966PubMedGoogle Scholar
  152. 152.
    Brackertz M, Gong Z, Leers J, Renkawitz R (2006) p66alpha and p66beta of the Mi-2/NuRD complex mediate MBD2 and histone interaction. Nucleic Acids Res 34:397–406PubMedCentralPubMedGoogle Scholar
  153. 153.
    Gong Z, Brackertz M, Renkawitz R (2006) SUMO modification enhances p66-mediated transcriptional repression of the Mi-2/NuRD complex. Mol Cell Biol 26:4519–4528PubMedCentralPubMedGoogle Scholar
  154. 154.
    Tsuji T et al (1998) Cloning, mapping, expression, function, and mutation analyses of the human ortholog of the hamster putative tumor suppressor gene Doc-1. J Biol Chem 273:6704–6709PubMedGoogle Scholar
  155. 155.
    Yuan Z, Sotsky Kent T, Weber TK (2003) Differential expression of DOC-1 in microsatellite-unstable human colorectal cancer. Oncogene 22:6304–6310PubMedGoogle Scholar
  156. 156.
    Spruijt CG et al (2010) CDK2AP1/DOC-1 is a bona fide subunit of the Mi-2/NuRD complex. Mol BioSyst 6:1700–1706PubMedGoogle Scholar
  157. 157.
    Shintani S et al (2000) p12(DOC-1) is a novel cyclin-dependent kinase 2-associated protein. Mol Cell Biol 20:6300–6307PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Morgan P. Torchy
    • 1
    • 2
    • 3
    • 4
  • Ali Hamiche
    • 1
    • 2
    • 3
    • 4
  • Bruno P. Klaholz
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of Integrated Structural Biology, Centre for Integrative Biology (CBI)Institute of Genetics and of Molecular and Cellular Biology (IGBMC)IllkirchFrance
  2. 2.Centre National de la Recherche Scientifique (CNRS) UMR 7104IllkirchFrance
  3. 3.Institut National de la Santé et de la Recherche Médicale (INSERM) U964IllkirchFrance
  4. 4.Université de StrasbourgStrasbourgFrance

Personalised recommendations