title: Histone acetylation contributes to chromatin looping between the locus control region and globin gene by influencing hypersensitive site formation.
abstract: Chromatin loops are formed between enhancers and promoters and between insulators to regulate gene transcription in the eukaryotic genome. These transcription regulatory elements forming loops have highly acetylated histones. To understand the correlation between histone acetylation and chromatin loop formation, we inhibited the expression of histone acetyltransferase CBP and p300 in erythroid K562 cells and analyzed the chromatin structure of the β-globin locus. The proximity between the locus control region (LCR) and the active (G)γ-globin gene was decreased in the β-globin locus when histones were hypoacetylated by the double knockdown of CBP and p300. Sensitivity to DNase I and binding of erythroid specific activators were reduced in the hypoacetylated LCR hypersensitive sites (HSs) and gene promoter. Interestingly, the chromatin loop between HS5 and 3'HS1 was formed regardless of the hypoacetylation of the β-globin locus. CTCF binding was maintained at HS5 and 3'HS1 in the hypoacetylated locus. Thus, these results indicate that histone acetylation contributes to chromatin looping through the formation of HSs in the LCR and gene promoter. However, looping between insulators appears to be independent from histone acetylation.
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan, South Korea.
authors.forename: Yea Woon
authors.initials: YW
authors.lastname: Kim
authors.forename: AeRi
authors.initials: A
authors.lastname: Kim
mesh_terms: D000107:Acetylation; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005914:Globins / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D019901:Locus Control Region; D008745:Methylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050880:p300-CBP Transcription Factors / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; D005914:Globins; D050880:p300-CBP Transcription Factors
keywords: 3C; ChIP; Chromatin loop; HAT; HS; Histone acetylation; Hypersensitive site; LCR; RT-PCR; Transcription; chromatin immunoprecipitation; chromosome conformation capture; histone acetyltransferase; hypersensitive site; locus control region; reverse transcription-PCR; shRNA; short hairpin RNA; β-Globin locus