Histone Acetylation: Long‐range Patterns in the Genome

Abstract

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 transcription factor (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 bromodomain‐containing coactivators (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.

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Further Reading

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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]