Nucleosome and transcription activator antagonism at human beta-globin locus control region DNase I hypersensitive sites.
Nucleosome and transcription activator antagonism at human beta-globin locus control region DNase I hypersensitive sites.
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DOI：
10.1093/nar/gkm620
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发表时间：
2007
影响因子：
14.9
通讯作者：
Dean, Ann
中科院分区：
文献类型：
--
作者：
Kim, AeRi;Song, Sang-hyun;Brand, Marjorie;Dean, Ann
基因座控制区是激活远端基因的调控元件，通常由与转录激活因子结合位点簇一致的几个DNase I超敏感位点组成。核小体和激活剂在多大程度上共同或单独占据这些位点尚未在体内进行广泛研究。我们分析了表达胚胎和胎儿珠蛋白基因的红系细胞中人β-珠蛋白基因座控制区超敏位点的染色质结构。核小体在超敏位点HS 1-HS 4和5′侧翼的HS 5处被耗尽。代替核小体，活化剂与这些位点差异相关。红细胞特异性加塔-1位于HS 1、HS 2和HS 4，但NF-E2异源二聚体仅限于核小体最严重耗尽的HS 2。组蛋白H3和H4在整个LCR的K4处被过度乙酰化，并且H3在K4处被二甲基化，然而，H3 K4 MLL甲基转移酶组分Ash 2L和组蛋白乙酰转移酶CBP和p300基本上仅占据HS 2，并且HS 2中的NF-E2基序是Ash 2L募集所需的。我们的研究结果表明，在人类β-珠蛋白LCR中的每个超敏位点具有独特的结构特征，并表明HS 2在珠蛋白基因表达的胚胎和胎儿阶段的LCR组织中起着关键作用。
Locus control regions are regulatory elements that activate distant genes and typically consist of several DNase I hypersensitive sites coincident with clusters of transcription activator binding sites. To what extent nucleosomes and activators occupy these sites together or exclusively has not been extensively studied in vivo. We analyzed the chromatin structure of human β-globin locus control region hypersensitive sites in erythroid cells expressing embryonic and fetal globin genes. Nucleosomes were variably depleted at hypersensitive sites HS1-HS4 and at HS5 which flanks the 5′ of the locus. In lieu of nucleosomes, activators were differentially associated with these sites. Erythroid–specific GATA-1 resided at HS1, HS2 and HS4 but the NF-E2 hetero-dimer was limited to HS2 where nucleosomes were most severely depleted. Histones H3 and H4 were hyperacetylated and H3 was di-methylated at K4 across the LCR, however, the H3 K4 MLL methyltransferase component Ash2L and histone acetyltransferases CBP and p300 occupied essentially only HS2 and the NF-E2 motif in HS2 was required for Ash2L recruitment. Our results indicate that each hypersensitive site in the human β-globin LCR has distinct structural features and suggest that HS2 plays a pivotal role in LCR organization at embryonic and fetal stages of globin gene expression.