Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
PLoS Genet. 2012;8(7):e1002811. doi: 10.1371/journal.pgen.1002811. Epub 2012 Jul 12.
Chd proteins are ATP-dependent chromatin remodeling enzymes implicated in biological functions from transcriptional elongation to control of pluripotency. Previous studies of the Chd1 subclass of these proteins have implicated them in diverse roles in gene expression including functions during initiation, elongation, and termination. Furthermore, some evidence has suggested a role for Chd1 in replication-independent histone exchange or assembly. Here, we examine roles of Chd1 in replication-independent dynamics of histone H3 in both Drosophila and yeast. We find evidence of a role for Chd1 in H3 dynamics in both organisms. Using genome-wide ChIP-on-chip analysis, we find that Chd1 influences histone turnover at the 5' and 3' ends of genes, accelerating H3 replacement at the 5' ends of genes while protecting the 3' ends of genes from excessive H3 turnover. Although consistent with a direct role for Chd1 in exchange, these results may indicate that Chd1 stabilizes nucleosomes perturbed by transcription. Curiously, we observe a strong effect of gene length on Chd1's effects on H3 turnover. Finally, we show that Chd1 also affects histone modification patterns over genes, likely as a consequence of its effects on histone replacement. Taken together, our results emphasize a role for Chd1 in histone replacement in both budding yeast and Drosophila melanogaster, and surprisingly they show that the major effects of Chd1 on turnover occur at the 3' ends of genes.
Chd 蛋白是依赖于 ATP 的染色质重塑酶,参与从转录延伸到多能性控制的生物学功能。这些蛋白质的 Chd1 亚类的先前研究表明它们在基因表达的多种作用中发挥作用,包括在起始、延伸和终止过程中的功能。此外,一些证据表明 Chd1 在复制独立的组蛋白交换或组装中起作用。在这里,我们研究了 Chd1 在果蝇和酵母中复制独立的组蛋白 H3 动力学中的作用。我们发现 Chd1 在这两种生物中都参与了 H3 动力学。通过全基因组 ChIP-on-chip 分析,我们发现 Chd1 影响基因 5' 和 3' 端的组蛋白周转率,加速基因 5' 端的 H3 替换,同时保护基因 3' 端免受过度的 H3 周转率。虽然这与 Chd1 在交换中的直接作用一致,但这些结果可能表明 Chd1 稳定了转录引起的核小体扰动。奇怪的是,我们观察到基因长度对 Chd1 对 H3 周转率的影响有很强的影响。最后,我们表明 Chd1 还影响基因上的组蛋白修饰模式,这可能是其对组蛋白替换的影响的结果。总之,我们的结果强调了 Chd1 在芽殖酵母和黑腹果蝇中组蛋白替换中的作用,令人惊讶的是,它们表明 Chd1 对周转率的主要影响发生在基因的 3' 端。