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Transcription-coupled deposition of histone modifications during MHC class II gene activation

机译:MHC II类基因激活过程中组蛋白修饰的转录偶联沉积

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摘要

Posttranslational histone modifications associated with actively expressed genes are generally believed to be introduced primarily by histone-modifying enzymes that are recruited by transcription factors or their associated co-activators. We have performed a comprehensive spatial and temporal analyses of the histone modifications that are deposited upon activation of the MHC class II gene HLA-DRA by the co-activator CIITA. We find that transcription-associated histone modifications are introduced during two sequential phases. The first phase precedes transcription initiation and is characterized exclusively by a rapid increase in histone H4 acetylation over a large upstream domain. All other modifications examined, including the acetylation and methylation of several residues in histone H3, are restricted to short regions situated at or within the 5′ end of the gene and are established during a second phase that is concomitant with ongoing transcription. This second phase is completely abrogated when elongation by RNA polymerase II is blocked. These results provide strong evidence that transcription elongation can play a decisive role in the deposition of histone modification patterns associated with inducible gene activation.
机译:通常认为,与活跃表达的基因相关的翻译后组蛋白修饰主要是由组蛋白修饰酶引入的,而该组蛋白修饰酶是由转录因子或其相关的共激活因子募集的。我们已经对组蛋白修饰进行了全面的时空分析,该组蛋白修饰是由共激活因子CIITA激活II类MHC基因HLA-DRA激活的。我们发现,转录相关的组蛋白修饰是在两个连续的阶段引入的。第一阶段在转录起始之前,其特征仅在于在较大的上游结构域中组蛋白H4乙酰化的快速增加。检查的所有其他修饰,包括组蛋白H3中几个残基的乙酰化和甲基化,均限于位于基因5'端或5'端的短区,并在与正在进行的转录相伴的第二阶段建立。当RNA聚合酶II的延伸被阻断时,该第二阶段被完全废除。这些结果提供了有力的证据,证明转录延长可以在与诱导型基因激活相关的组蛋白修饰模式的沉积中起决定性作用。

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