Chd1 co-localizes with early transcription elongation factors independently of H3K36 methylation and releases stalled RNA polymerase II at introns.
Chd1 co-localizes with early transcription elongation factors independently of H3K36 methylation and releases stalled RNA polymerase II at introns.
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DOI：
10.1186/1756-8935-7-32
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发表时间：
2014
影响因子：
3.9
通讯作者：
Iyer VR
中科院分区：
文献类型：
--
作者：
Park D;Shivram H;Iyer VR
染色质由高度保守的三磷酸腺苷（ATP）依赖性染色质重塑复合物控制的有序核小体阵列组成。一种这样的重塑剂，染色体结构域解旋酶DNA结合蛋白1（Chd 1），被认为在核小体组织中发挥不可或缺的作用，因为已知Chd 1的丢失会破坏染色质。然而，Chd 1在染色质上的功能和物理定位的特异性和基础在很大程度上仍然未知。使用全基因组的方法，我们发现，Chd 1的损失显着破坏核小体阵列内的基因体的高度转录的基因。我们还发现，Chd 1是物理招募的基因体，其占用率具体对应于RNA聚合酶，RNAPII丝氨酸5-P的早期延伸形式。相反，RNAPII丝氨酸5-P占用率受到Chd 1的损失，这表明Chd 1与早期转录延伸。令人惊讶的是，RNAPII Ser 5-P的占用受到Chd 1缺失的影响，特别是在含内含子的基因处。核小体营业额也受到影响，在这些网站的情况下，Chd 1。我们还发现，删除组蛋白甲基转移酶H3 K36（SET 2）不影响Chd 1占用或核小体组织全基因组。Chd 1是专门招募到高度转录基因的基因体中的延伸依赖性，但H3 K36 me 3独立的方式。Chd 1与RNA聚合酶的早期延伸形式共定位，并且仅在含有内含子的基因处影响RNAPII的占用，这表明在缓解RNAPII的剪接相关暂停中的作用。本文的在线版本（doi：10.1186/1756-8935-7-32）包含补充材料，可供授权用户使用。
Chromatin consists of ordered nucleosomal arrays that are controlled by highly conserved adenosine triphosphate (ATP)-dependent chromatin remodeling complexes. One such remodeler, chromodomain helicase DNA binding protein 1 (Chd1), is believed to play an integral role in nucleosomal organization, as the loss of Chd1 is known to disrupt chromatin. However, the specificity and basis for the functional and physical localization of Chd1 on chromatin remains largely unknown. Using genome-wide approaches, we found that the loss of Chd1 significantly disrupted nucleosome arrays within the gene bodies of highly transcribed genes. We also found that Chd1 is physically recruited to gene bodies, and that its occupancy specifically corresponds to that of the early elongating form of RNA polymerase, RNAPII Ser 5-P. Conversely, RNAPII Ser 5-P occupancy was affected by the loss of Chd1, suggesting that Chd1 is associated with early transcription elongation. Surprisingly, the occupancy of RNAPII Ser 5-P was affected by the loss of Chd1 specifically at intron-containing genes. Nucleosome turnover was also affected at these sites in the absence of Chd1. We also found that deletion of the histone methyltransferase for H3K36 (SET2) did not affect either Chd1 occupancy or nucleosome organization genome-wide. Chd1 is specifically recruited onto the gene bodies of highly transcribed genes in an elongation-dependent but H3K36me3-independent manner. Chd1 co-localizes with the early elongating form of RNA polymerase, and affects the occupancy of RNAPII only at genes containing introns, suggesting a role in relieving splicing-related pausing of RNAPII. The online version of this article (doi:10.1186/1756-8935-7-32) contains supplementary material, which is available to authorized users.
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