Kim Yea Woon, Kim AeRi
Department of Molecular Biology, Pusan National University, Busan, South Korea.
Biochim Biophys Acta. 2013 Sep;1829(9):963-9. doi: 10.1016/j.bbagrm.2013.04.006. Epub 2013 Apr 20.
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.
染色质环在增强子与启动子之间以及绝缘子之间形成，以调控真核生物基因组中的基因转录。形成环的这些转录调控元件具有高度乙酰化的组蛋白。为了理解组蛋白乙酰化与染色质环形成之间的相关性，我们抑制了红系K562细胞中组蛋白乙酰转移酶CBP和p300的表达，并分析了β-珠蛋白基因座的染色质结构。当通过CBP和p300的双敲低使组蛋白低乙酰化时，β-珠蛋白基因座中基因座控制区（LCR）与活性（G）γ-珠蛋白基因之间的距离减小。低乙酰化的LCR超敏位点（HSs）和基因启动子对DNase I的敏感性以及红系特异性激活剂的结合减少。有趣的是，无论β-珠蛋白基因座是否低乙酰化，HS5和3'HS1之间的染色质环都会形成。在低乙酰化的基因座中，CTCF在HS5和3'HS1处的结合得以维持。因此，这些结果表明组蛋白乙酰化通过在LCR和基因启动子中形成HSs促进染色质环化。然而，绝缘子之间的环化似乎独立于组蛋白乙酰化。
