Histone H1 represses estrogen receptor α transcriptional activity by selectively inhibiting receptor-mediated transcription initiation
Histone H1 represses estrogen receptor α transcriptional activity by selectively inhibiting receptor-mediated transcription initiation
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DOI：
10.1128/mcb.22.8.2463-2471.2002
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发表时间：
2002-04-01
影响因子：
5.3
通讯作者：
Kraus, WL
中科院分区：
文献类型：
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作者：
Cheung, E;Zarifyan, AS;Kraus, WL
在真核生物中，染色质是许多核过程的生理模板，包括RNA聚合酶h的转录。在体内，染色质由基因组DNA、核心组蛋白、连接组蛋白（如组蛋白H1）和非组蛋白染色质相关蛋白组装而成。组蛋白H1被认为是通过促进染色质压缩成高阶结构而作为转录的一般抑制因子。我们使用生化方法，包括体外染色质组装和转录系统，来检查组蛋白H1对雌激素受体α (er α)介导的染色质模板转录的影响。我们发现组蛋白H1作为一种有效的阻遏因子，可以抑制配体和辅激活因子调节的er α转录。组蛋白H1发挥其抑制作用，但不抑制er - α与染色质的序列特异性结合，也不抑制共激活子p300靶向核小体组蛋白乙酰化的总体程度。相反，组蛋白H1通过阻断erα依赖性转录过程中的特定步骤，即转录起始，而不影响转录再起始。总之，我们的数据表明，组蛋白H1通过限制启动子的可及性和阻止erα依赖性的稳定转录起始前复合物的形成，选择性地降低了有效转录起始的总体水平。
Chromatin is the physiological template for many nuclear processes in eukaryotes, including transcription by RNA polymerase H. In vivo, chromatin is assembled from genomic DNA, core histones, linker histones such as histone H1, and nonhistone chromatin-associated proteins. Histone H1 is thought to act as a general repressor of transcription by promoting the compaction of chromatin into higher-order structures. We have used a biochemical approach, including an in vitro chromatin assembly and transcription system, to examine the effects of histone H1 on estrogen receptor alpha (ERalpha)-mediated transcription with chromatin templates. We show that histone H1 acts as a potent repressor of ligand- and coactivator-regulated transcription by ERalpha. Histone H1 exerts its repressive effect without inhibiting the sequence-specific binding of ERalpha to chromatin or the overall extent of targeted acetylation of nucleosomal histones by the coactivator p300. Instead, histone H1 acts by blocking a specific step in the ERalpha-dependent transcription process, namely, transcription initiation, without affecting transcription reinitiation. Together, our data indicate that histone H1 acts selectively to reduce the overall level of productive transcription initiation by restricting promoter accessibility and preventing the ERalpha-dependent formation of a stable transcription preinitiation complex.