Department of Molecular genetics, Weizmann Institute of Science, Herzl street, Rehovot 76100, Israel.
Genome Biol. 2010;11(5):R49. doi: 10.1186/gb-2010-11-5-r49. Epub 2010 May 10.
The positions of nucleosomes along eukaryotic DNA are defined by the local DNA sequence and are further tuned by the activity of chromatin remodelers. While the genome-wide effect of most remodelers has not been described, recent studies in Saccharomyces cerevisiae have shown that Isw2 prevents ectopic expression of anti-sense and suppressed transcripts at gene ends.
We examined the genome-wide function of the Isw2 homologue, Isw1, by mapping nucleosome positioning in S. cerevisiae and Saccharomyces paradoxus strains deleted of ISW1. We found that Isw1 functions primarily within coding regions of genes, consistent with its putative role in transcription elongation. Upon deletion of ISW1, mid-coding nucleosomes were shifted upstream (towards the 5' ends) in about half of the genes. Isw1-dependent shifts were correlated with trimethylation of H3K79 and were enriched at genes with internal cryptic initiation sites.
Our results suggest a division of labor between Isw1 and Isw2, whereby Isw2 maintains repressive chromatin structure at gene ends while Isw1 has a similar function at mid-coding regions. The differential specificity of the two remodelers may be specified through interactions with particular histone marks.
真核生物 DNA 上核小体的位置由局部 DNA 序列决定，并进一步由染色质重塑剂的活性进行微调。虽然大多数重塑剂的全基因组效应尚未被描述，但最近在酿酒酵母中的研究表明，Isw2 可防止反义基因和基因末端被抑制转录本的异位表达。
我们通过在酿酒酵母和 S. paradoxus 缺失 ISW1 的菌株中绘制核小体定位，研究了 Isw2 同源物 Isw1 的全基因组功能。我们发现，Isw1 主要在基因的编码区内发挥作用，与其在转录延伸中的潜在作用一致。在缺失 ISW1 后，大约一半基因的中编码核小体被向前（向 5' 端）移动。Isw1 依赖性的移动与 H3K79 的三甲基化有关，并且在具有内部隐蔽起始位点的基因中富集。
我们的结果表明，Isw1 和 Isw2 之间存在分工，Isw2 在基因末端维持抑制性染色质结构，而 Isw1 在中编码区具有类似的功能。两种重塑剂的差异特异性可能通过与特定组蛋白标记的相互作用来指定。
