Histone Acetylation: Long‐range Patterns in the Genome


Modification of core histones by acetylation establishes a chromatin environment permissive for gene expression. Complex patterns of acetylation spanning many kilobases have been identified at certain loci. However, little is known about the regulation and functional consequences of these broad domains of acetylation.

Keywords: histone; acetylation; chromatin; chromosome; epigenetics; transcription

Figure 1.

Regulation of transcriptional activation by localized histone acetylation. The model depicts specific regulatory steps that control transcription initiation. (a) A (TF) binds to DNA with sequence specificity and assembles into a stable nucleoprotein complex. For simplicity, only a single factor is shown. (b) The DNA‐bound factor physically associates with a component of a coactivator complex, thereby recruiting the complex to the chromatin template. (c) In the case of histone acetylase/acetyltransferases (HATs), this would result in easy access of the HAT to the neighboring chromatin and acetylation of the N‐terminal tails of core histones. Histone acetylation exerts at least three functional consequences. Acetylation increases the accessibility of nucleosomal DNA to additional binding factors and also interferes with higher‐order chromatin folding, which effectively increases DNA accessibility. (d) Bromodomain‐containing proteins, which are often coactivators, selectively recognize the acetylated N‐terminal tail of histone H4. Such (BD) might engage in further chromatin remodeling or protein–protein interactions that facilitate the recruitment of the transcriptional machinery. Although the model focuses on the actions of HATs to acetylate chromatin near the site of recruitment, nothing is known about the limits of the chromatin region that would be modified by this type of mechanism. AC: acetylated lysine.

Figure 2.

Broad histone acetylation patterns of the chicken β‐globin, mouse β‐globin, human α‐globin and human growth hormone (GH) loci. Histone acetylation of the various loci measured by chromatin immunoprecipitation assay. The levels of acetylation at a given locus are expressed as relative units and are not comparable with other loci. (a) Multiacetylated histone H3 of the endogenous chicken β‐globin locus in embryonic red blood cells. (b) Multiacetylated histone H3 of the endogenous murine β‐globin locus in mouse erythroleukemia cells. (c) Lysine 5 acetylated H4 of the endogenous human α‐globin locus in primary erythroid progenitor cells. (d) Multiacetylated histones H3 and H4 of the human GH locus in pituitaries of transgenic mice. FR: folate receptor gene; LCR: locus control region; MRE: major regulatory element.



Allfrey V, Faulkner RM and Mirsky AE (1964) Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proceedings of the National Academy of Sciences of the United States of America 51: 786–794.

Anguita E, Johnson CA, Wood WG, Turner BM and Higgs DR (2001) Identification of a conserved erythroid‐specific domain of histone acetylation across the alpha‐globin gene cluster. Proceedings of the National Academy of Sciences of the United States of America 98: 12114–12119.

Durrin LK, Mann RK, Kayne PS and Grunstein M (1991) Yeast histone H4 N‐terminal sequence is required for promoter activation in vivo. Cell 65: 1023–1031.

Elefant F, Cooke NE and Liebhaber SA (2000) Targeted recruitment of histone acetyltransferase activity to a locus control region. Journal of Biological Chemistry 275: 13827–13834.

Forsberg EC and Bresnick EH (2001) Histone acetylation beyond promoters: long‐range acetylation patterns in the chromatin world. Bioessays 23: 820–830.

Forsberg EC, et al. (2000) Developmentally dynamic histone acetylation pattern of a tissue‐specific chromatin domain. Proceedings of the National Academy of Sciences of the United States of America 97: 14494–14499.

Hebbes TR, Clayton AL, Thorne AW and Crane‐Robinson C (1994) Core histone hyperacetylation co‐maps with generalized DNase I sensitivity in the chicken beta‐globin chromosomal domain. EMBO Journal 13: 1823–1830.

Jacobson RH, Ladurner AG, King DS and Tjian R (2000) Structure and function of a human TAFII250 double bromodomain module. Science 288: 1422–1425.

Johnson KD, Christensen HM, Zhao B and Bresnick EH (2001) Distinct mechanisms control RNA polymerase II recruitment to a tissue‐specific locus control region and a downstream promoter. Molecular Cell 8: 465–471.

Laherty CD, Yang WM, Sun JM, et al. (1997) Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression. Cell 89: 349–356.

Lee DY, Hayes JJ, Pruss D and Wolffe AP (1993) A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell 72: 73–84.

Litt MD, Simpson M, Recillas‐Targa F, Prioleau MN and Felsenfeld G (2001) Transitions in histone acetylation reveal boundaries of three separately regulated neighboring loci. EMBO Journal 20: 2224–2235.

Schubeler D, Francastel C, Cimbora DM, et al. (2000) Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human beta‐globin locus. Genes & Development 14: 940–950.

Strahl BD and Allis CD (2000) The language of covalent histone modifications. Nature 403: 41–45.

Tse C, Sera T, Wolffe AP and Hansen JC (1998) Disruption of higher‐order folding by core histone acetylation dramatically enhances transcription of nucleosomal arrays by RNA polymerase III. Molecular Cell Biology 18: 4629–4638.

Further Reading

Brownell JE, Zhou J, Ranalli T, et al. (1996) Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84: 843–851.

Bulger M and Groudine M (1999) Looping versus linking: toward a model for long‐distance gene activation. Genes & Development 13: 2465–2477.

Elefant F, Su Y, Liebhaber SA and Cooke NE (2000) Patterns of histone acetylation suggest dual pathways for gene activation by a bifunctional locus control region. EMBO Journal 19: 6814–6822.

Schubeler D, Groudine M and Bender MA (2001) The murine beta‐globin locus control region regulates the rate of transcription but not the hyperacetylation of histones at the active genes. Proceedings of the National Academy of Sciences of the United States of America 11: 11.

Vettese‐Dadey M, Grant PA, Hebbes TR, et al. (1996) Acetylation of histone H4 plays a primary role in enhancing transcription factor binding to nucleosomal DNA in vitro. EMBO Journal 15: 2508–2518.

Web Links

CSHL1(chorionic somatomammotropin hormone‐like 1); LocusID: 1442. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1442

GH1 (growth hormone 1); LocusID: 2688. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2688

CSHL1(chorionic somatomammotropin hormone‐like 1); MIM number: 150200. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?150200

GH1 (growth hormone 1); MIM number: 139250. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?139250

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Bresnick, Emery H, Im, Hogune, and Johnson, Kirby D(Jan 2006) Histone Acetylation: Long‐range Patterns in the Genome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005987]