Distinct mechanisms control RNA polymerase II recruitment to a tissue-specific locus control region and a downstream promoter
Distinct mechanisms control RNA polymerase II recruitment to a tissue-specific locus control region and a downstream promoter
复制标题
DOI：
10.1016/s1097-2765(01)00309-4
复制
发表时间：
2001-08-01
期刊：
影响因子：
16
通讯作者：
Bresnick, EH
中科院分区：
文献类型：
--
作者：
Johnson, KD;Christensen, HM;Bresnick, EH
组蛋白乙酰化先于许多基因的激活。然而，远程乙酰化模式的建立和后果知之甚少。为了确定β-珠蛋白基因座的发育动态组蛋白乙酰化模式的分子决定因素，我们比较了MEL和CB 3红白血病细胞中基因座的乙酰化。CB 3细胞缺乏β-珠蛋白基因座控制区（LCR）结合蛋白p45/ NF-E2。我们发现，p45/NF-E2是成人β-珠蛋白启动子处组蛋白超乙酰化所必需的，类似于LCR下游的50个乙酰化酶，但不是在LCR处。令人惊讶的是，RNA聚合酶II以p45/NF-E2非依赖性方式与LCR相关，而其募集到启动子需要p45/NF-E2。我们提出，聚合酶访问LCR和p45/ NF-E2诱导聚合酶的远程转移到启动子，导致转录激活。
Histone acetylation precedes activation of many genes. However, the establishment and consequences of long-range acetylation patterns are poorly understood. To define molecular determinants of the developmentally dynamic histone acetylation pattern of the beta -globin locus, we compared acetylation of the locus in MEL and CB3 erythroleukemia cells. CB3 cells lack the beta -globin locus control region (LCR) binding protein p45/ NF-E2. We found that p45/NF-E2 was required for histone hyperacetylation at adult beta -globin promoters similar to 50 kilobases downstream of the LCR, but not at the LCR. Surprisingly, RNA polymerase II associated with the LCR in a p45/NF-E2-independent manner, while its recruitment to the promoter required p45/NF-E2. We propose that polymerase accesses the LCR and p45/ NF-E2 induces long-range transfer of polymerase to the promoter, resulting in transcriptional activation.