Human SWI/SNF directs sequence-specific chromatin changes on promoter polynucleosomes.
Human SWI/SNF directs sequence-specific chromatin changes on promoter polynucleosomes.
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人类 SWI/SNF 指导启动子多核小体上的序列特异性染色质变化。
DOI：
10.1093/nar/gkn623
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发表时间：
2008
影响因子：
14.9
通讯作者：
Schnitzler,GavinR
中科院分区：
文献类型：
--
作者：
Sims,HillelI;Baughman,CassandraB;Schnitzler,GavinR
对人类和其他物种的研究表明，令人惊讶的是，很大一部分核小体采用启动子上的特定位置，这些位置似乎是由核小体定位DNA序列（nps）决定的。我们实验室最近的研究表明，人类SWI/SNF复合物（hSWI/SNF）倾向于将核小体从nps中重新定位。我们现在利用新的作图技术来研究多核体染色质背景下hSWI/SNF序列对核小体运动的偏好，其中相邻的核小体可以限制运动，hSWI/SNF形成改变的二核小体结构。使用两个NPS模板（5S rDNA和601）和两个hSWI/SNF靶启动子模板（c-myc和UGT1A1），我们观察到hSWI/SNF驱动的正常单核小体几乎从所有被组装强烈支持的位置消失。在某些情况下，这些单核小体被移动到hSWI/ snf首选序列。在大多数其他情况下，一个重新定位的单核小体似乎与一个未移动的单核小体结合，形成一个特异性定位的改变或正常的二核小体。这些影响导致核小体分布发生显著的模板特异性变化。综上所述，这些研究表明hSWI/SNF可能通过在染色质结构中产生启动子序列特异性改变来激活或抑制其靶基因的转录。
Studies in humans and other species have revealed that a surprisingly large fraction of nucleosomes adopt specific positions on promoters, and that these positions appear to be determined by nucleosome positioning DNA sequences (NPSs). Recent studies by our lab, using minicircles containing only one nucleosome, indicated that the human SWI/SNF complex (hSWI/SNF) prefers to relocate nucleosomes away from NPSs. We now make use of novel mapping techniques to examine the hSWI/SNF sequence preference for nucleosome movement in the context of polynucleosomal chromatin, where adjacent nucleosomes can limit movement and where hSWI/SNF forms altered dinucleosomal structures. Using two NPS templates (5S rDNA and 601) and two hSWI/SNF target promoter templates (c-myc and UGT1A1), we observed hSWI/SNF-driven depletion of normal mononucleosomes from almost all positions that were strongly favored by assembly. In some cases, these mononucleosomes were moved to hSWI/SNF-preferred sequences. In the majority of other cases, one repositioned mononucleosome appeared to combine with an unmoved mononucleosome forming a specifically localized altered or normal dinucleosome. These effects result in dramatic, template-specific changes in nucleosomal distribution. Taken together, these studies indicate hSWI/SNF is likely to activate or repress transcription of its target genes by generating promoter sequence-specific changes in chromatin configuration.