Skip to main content
SpringerLink
Log in

Control of gene expression and assembly of chromosomal subdomains by chromatin regulators with antagonistic functions

  • Mini-Review
  • Published:
Chromosoma Aims and scope Submit manuscript

Abstract

Epigenetic regulation of higher-order chromatin structure controls gene expression and the assembly of chromosomal domains during cell division, differentiation, and development. The proposed “histone code” integrates a complex system of histone modifications and chromosomal proteins that establish and maintain distinctive types of chromatin, such as euchromatin, heterochromatin, and centromeric (CEN) chromatin. The reversible nature of histone acetylation, phosphorylation, and (most recently discovered) methylation are mechanisms for controlling gene expression and partitioning the genome into functional domains. Many different regions of the genome contain similar epigenetic marks (histone modifications), raising the question as to how they are independently specified and regulated. In this review, we will focus on several recent discoveries in chromatin and chromosome biology: (1) identification of long-elusive histone “de-methylating” enzymes that affect chromatin structure, and (2) assembly and maintenance of chromatin domains, specifically heterochromatin and euchromatin, through a dynamic equilibrium of modifying enzymes, histone modifications, and histone variants identified biochemically and genetically.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Allis CD, Bowen JK, Abraham GN, Glover CV, Gorovsky MA (1980) Proteolytic processing of histone H3 in chromatin: a physiologically regulated event in tetrahymena micronuclei. Cell 20:55–64

    Article  PubMed  CAS  Google Scholar 

  • Allshire RC, Javerzat JP, Redhead NJ, Cranston G (1994) Position effect variegation at fission yeast centromeres. Cell 76:157–169

    Article  PubMed  CAS  Google Scholar 

  • Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T (2001) Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410:120–124

    Article  PubMed  CAS  Google Scholar 

  • Bannister AJ, Schneider R, Kouzarides T (2002) Histone methylation: dynamic or static? Cell 109:801–806

    Article  PubMed  CAS  Google Scholar 

  • Bauer UM, Daujat S, Nielsen SJ, Nightingale K, Kouzarides T (2002) Methylation at arginine 17 of histone H3 is linked to gene activation. EMBO Rep 3:39–44

    Article  PubMed  CAS  Google Scholar 

  • Blower MD, Sullivan BA, Karpen GH (2002) Conserved organization of centromeric chromatin in flies and humans. Dev Cell 2:319–330

    Article  PubMed  CAS  Google Scholar 

  • Carrel L, Willard HF (2005) X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434:400–404

    Article  PubMed  CAS  Google Scholar 

  • Chadwick BP, Willard HF (2004) Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome. Proc Natl Acad Sci U S A 101:17450–17455

    Article  PubMed  CAS  Google Scholar 

  • Cheutin T, McNairn AJ, Jenuwein T, Gilbert DM, Singh PB, Misteli T (2003) Maintenance of stable heterochromatin domains by dynamic HP1 binding. Science 299:721–725

    Article  PubMed  CAS  Google Scholar 

  • Chueh AC, Wong LH, Wong N, Choo KH (2005) Variable and hierarchical size distribution of L1-retroelement-enriched CENP-A clusters within a functional human neocentromere. Hum Mol Genet 14:85–93

    Article  PubMed  CAS  Google Scholar 

  • Cleard F, Delattre M, Spierer P (1997) SU(VAR)3-7, a Drosophila heterochromatin-associated protein and companion of HP1 in the genomic silencing of position–effect variegation. EMBO J 16:5280–5288

    Article  PubMed  CAS  Google Scholar 

  • Cuthbert GL, Daujat S, Snowden AW, Erdjument-Bromage H, Hagiwara T, Yamada M, Schneider R, Gregory PD, Tempst P, Bannister AJ, Kouzarides T (2004) Histone deimination antagonizes arginine methylation. Cell 118:545–553

    Article  PubMed  CAS  Google Scholar 

  • Ebert A, Schotta G, Lein S, Kubicek S, Krauss V, Jenuwein T, Reuter G (2004) Su(var) genes regulate the balance between euchromatin and heterochromatin in Drosophila. Genes Dev 18:2973–2983

    Article  PubMed  CAS  Google Scholar 

  • Ekwall K, Olsson T, Turner BM, Cranston G, Allshire RC (1997) Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell 91:1021–1032

    Article  PubMed  CAS  Google Scholar 

  • Fan JY, Rangasamy D, Luger K, Tremethick DJ (2004) H2A.Z alters the nucleosome surface to promote HP1alpha-mediated chromatin fiber folding. Mol Cell 16:655–661

    Article  PubMed  CAS  Google Scholar 

  • Fang J, Feng Q, Ketel CS, Wang H, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Simon JA, Zhang Y (2002) Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr Biol 12:1086–1099

    Article  PubMed  CAS  Google Scholar 

  • Fanti L, Giovinazzo G, Berloco M, Pimpinelli S (1998) The heterochromatin protein 1 prevents telomere fusions in Drosophila. Mol Cell 2:527–538

    Article  PubMed  CAS  Google Scholar 

  • Fischle W, Wang Y, Allis CD (2003a) Binary switches and modification cassettes in histone biology and beyond. Nature 425:475–479

    Article  PubMed  CAS  Google Scholar 

  • Fischle W, Wang Y, Allis CD (2003b) Histone and chromatin cross-talk. Curr Opin Cell Biol 15:172–183

    Article  PubMed  CAS  Google Scholar 

  • Grewal SI, Moazed D (2003) Heterochromatin and epigenetic control of gene expression. Science 301:798–802

    Article  PubMed  CAS  Google Scholar 

  • Grewal SI, Rice JC (2004) Regulation of heterochromatin by histone methylation and small RNAs. Curr Opin Cell Biol 16:230–238

    Article  PubMed  CAS  Google Scholar 

  • Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080

    Article  PubMed  CAS  Google Scholar 

  • Karpen GH (1994) Position–effect variegation and the new biology of heterochromatin. Curr Opin Genet Dev 4:281–291

    Article  PubMed  CAS  Google Scholar 

  • Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T (2001) Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410:116–120

    Article  PubMed  CAS  Google Scholar 

  • Lippman Z, Martienssen R (2004) The role of RNA interference in heterochromatic silencing. Nature 431:364–370

    Article  PubMed  CAS  Google Scholar 

  • Litt MD, Simpson M, Gaszner M, Allis CD, Felsenfeld G (2001) Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus. Science 293:2453–2455

    Article  PubMed  CAS  Google Scholar 

  • Maggert KA, Karpen GH (2001) The activation of a neocentromere in Drosophila requires proximity to an endogenous centromere. Genetics 158:1615–1628

    PubMed  CAS  Google Scholar 

  • Meneghini MD, Wu M, Madhani HD (2003) Conserved histone variant H2A.Z protects euchromatin from the ectopic spread of silent heterochromatin. Cell 112:725–736

    Article  PubMed  CAS  Google Scholar 

  • Muller HJ (1930) Types of visible variations induced by X-rays in Drosophila. J Genet 22:299–335

    Article  Google Scholar 

  • Nagaki K, Cheng Z, Ouyang S, Talbert PB, Kim M, Jones KM, Henikoff S, Buell CR, Jiang J (2004) Sequencing of a rice centromere uncovers active genes. Nat Genet 36:138–145

    Article  PubMed  CAS  Google Scholar 

  • Nishioka K, Rice JC, Sarma K, Erdjument-Bromage H, Werner J, Wang Y, Chuikov S, Valenzuela P, Tempst P, Steward R et al (2002) PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol Cell 9:1201–1213

    Article  PubMed  CAS  Google Scholar 

  • Peters AH, O'Carroll D, Scherthan H, Mechtler K, Sauer S, Schofer C, Weipoltshammer K, Pagani M, Lachner M, Kohlmaier A et al (2001) Loss of the suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 107:323–337

    Article  PubMed  CAS  Google Scholar 

  • Peters AH, Mermoud JE, O'Carroll D, Pagani M, Schweizer D, Brockdorff N, Jenuwein T (2002) Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin. Nat Genet 30:77–80

    Article  PubMed  CAS  Google Scholar 

  • Peters AH, Kubicek S, Mechtler K, O'Sullivan RJ, Derijck AA, Perez-Burgos L, Kohlmaier A, Opravil S, Tachibana M, Shinkai Y et al (2003) Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol Cell 12:1577–1589

    Article  PubMed  CAS  Google Scholar 

  • Rangasamy D, Berven L, Ridgway P, Tremethick DJ (2003) Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development. EMBO J 22:1599–1607

    Article  PubMed  CAS  Google Scholar 

  • Rea S, Eisenhaber F, O'Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, Allis CD, Jenuwein T (2000) Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406:593–599

    Article  PubMed  CAS  Google Scholar 

  • Rice JC, Nishioka K, Sarma K, Steward R, Reinberg D, Allis CD (2002) Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes. Genes Dev 16:2225–2230

    Article  PubMed  CAS  Google Scholar 

  • Rice JC, Briggs SD, Ueberheide B, Barber CM, Shabanowitz J, Hunt DF, Shinkai Y, Allis CD (2003) Histone methyltransferases direct different degrees of methylation to define distinct chromatin domains. Mol Cell 12:1591–1598

    Article  PubMed  CAS  Google Scholar 

  • Rougeulle C, Navarro P, Avner P (2003) Promoter-restricted H3 Lys 4 di-methylation is an epigenetic mark for monoallelic expression. Hum Mol Genet 12:3343–3348

    Article  PubMed  CAS  Google Scholar 

  • Rusche LN, Kirchmaier AL, Rine J (2003) The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae. Annu Rev Biochem 72:481–516

    Article  PubMed  CAS  Google Scholar 

  • Santos-Rosa H, Schneider R, Bannister AJ, Sherriff J, Bernstein BE, Emre NC, Schreiber SL, Mellor J, Kouzarides T (2002) Active genes are tri-methylated at K4 of histone H3. Nature 419:407–411

    Article  PubMed  CAS  Google Scholar 

  • Santos-Rosa H, Schneider R, Bernstein BE, Karabetsou N, Morillon A, Weise C, Schreiber SL, Mellor J, Kouzarides T (2003) Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin. Mol Cell 12:1325–1332

    Article  PubMed  CAS  Google Scholar 

  • Santos-Rosa H, Bannister AJ, Dehe PM, Geli V, Kouzarides T (2004) Methylation of H3 lysine 4 at euchromatin promotes Sir3p association with heterochromatin. J Biol Chem 279:47506–47512

    Article  PubMed  CAS  Google Scholar 

  • Sarg B, Helliger W, Talasz H, Koutzamani E, Lindner HH (2004) Histone H4 hyperacetylation precludes histone H4 lysine 20 trimethylation. J Biol Chem 279:53458–53464

    Article  PubMed  CAS  Google Scholar 

  • 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 6:73–77

    Article  PubMed  CAS  Google Scholar 

  • Schotta G, Ebert A, Krauss V, Fischer A, Hoffmann J, Rea S, Jenuwein T, Dorn R, Reuter G (2002) Central role of Drosophila SU(VAR)3-9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J 21:1121–1131

    Article  PubMed  CAS  Google Scholar 

  • Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G, Reinberg D, Jenuwein T (2004) A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev 18:1251–1262

    Article  PubMed  CAS  Google Scholar 

  • Schubeler D, MacAlpine DM, Scalzo D, Wirbelauer C, Kooperberg C, van Leeuwen F, Gottschling DE, O'Neill LP, Turner BM, Delrow J et al (2004) The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. Genes Dev 18:1263–1271

    Article  PubMed  Google Scholar 

  • Schultz J (1936) Variegation in Drosophila and the inert chromosomal regions. Proc Natl Acad Sci U S A 22:27–33

    Article  PubMed  CAS  Google Scholar 

  • Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941–953

    Article  PubMed  CAS  Google Scholar 

  • Silva J, Mak W, Zvetkova I, Appanah R, Nesterova TB, Webster Z, Peters AH, Jenuwein T, Otte AP, Brockdorff N (2003) Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Dev Cell 4:481–495

    Article  PubMed  CAS  Google Scholar 

  • Suka N, Luo K, Grunstein M (2002) Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin. Nat Genet 32:378–383

    Article  PubMed  CAS  Google Scholar 

  • Sullivan KF (2001) A solid foundation: functional specialization of centromeric chromatin. Curr Opin Genet Dev 11:182–188

    Article  PubMed  CAS  Google Scholar 

  • Sullivan BA, Karpen GH (2004) Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin. Nat Struct Mol Biol 11:1076–1083

    Article  PubMed  CAS  Google Scholar 

  • Swaminathan J, Baxter EM, Corces VG (2005) The role of histone H2Av variant replacement and histone H4 acetylation in the establishment of Drosophila heterochromatin. Genes Dev 19:65–76

    Article  PubMed  CAS  Google Scholar 

  • Tachibana M, Sugimoto K, Nozaki M, Ueda J, Ohta T, Ohki M, Fukuda M, Takeda N, Niida H, Kato H, Shinkai Y (2002) G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev 16:1779–1791

    Article  PubMed  CAS  Google Scholar 

  • Van Hooser AA, Ouspenski II, Gregson HC, Starr DA, Yen TJ, Goldberg ML, Yokomori K, Earnshaw WC, Sullivan KF, Brinkley BR (2001) Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A. J Cell Sci 114:3529–3542

    PubMed  Google Scholar 

  • Wang H, Cao R, Xia L, Erdjument-Bromage H, Borchers C, Tempst P, Zhang Y (2001a) Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. Mol Cell 8:1207–1217

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Zhang W, Jin Y, Johansen J, Johansen KM (2001b) The JIL-1 tandem kinase mediates histone H3 phosphorylation and is required for maintenance of chromatin structure in Drosophila. Cell 105:433–443

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y et al (2004) Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306:279–283

    Article  PubMed  MathSciNet  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dave Allis, Laura Rusche and Cyrus Vaziri for helpful discussions. We apologize to our colleagues whose studies on histone modifications and chromatin structure were not cited due to space limitations. Our research is supported by grants from the National Institutes of Health (GM069514) and a Basil O'Connor Award from the March of Dimes (5-FY04-29).

Author information

Authors and Affiliations

  1. Department of Genetics and Genomics, Boston University School of Medicine, 715 Albany Street, E-645, Boston, MA, 02118, USA

    Ai Leen Lam, Dorothy E. Pazin & Beth A. Sullivan

Authors
  1. Ai Leen Lam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dorothy E. Pazin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Beth A. Sullivan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Beth A. Sullivan.

Additional information

Communicated by D. Griffin.

Review related to the 15th International Chromosome Conference (ICC XV), held in September 2004, Brunel University, London, UK

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lam, A.L., Pazin, D.E. & Sullivan, B.A. Control of gene expression and assembly of chromosomal subdomains by chromatin regulators with antagonistic functions. Chromosoma 114, 242–251 (2005). https://doi.org/10.1007/s00412-005-0001-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00412-005-0001-0

Keywords

Search

Navigation