The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo.
The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo.
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DOI：
10.1093/nar/gkw068
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发表时间：
2016-06-02
影响因子：
14.9
通讯作者：
Clark DJ
中科院分区：
文献类型：
--
作者：
Ocampo J;Chereji RV;Eriksson PR;Clark DJ
三磷酸腺苷依赖性染色质重塑机器通过操纵染色质结构在基因调控中发挥核心作用。大多数基因在启动子处有一个核小体缺失区，以及一组与转录起始位点相对应的规则间隔核小体。在体外，三种已知的酵母核小体间距酶（CHD1， ISW1和ISW2）形成不同间距的阵列。我们使用全基因组核小体测序来确定这些酶在体内是否有不同的空间核小体。我们发现CHD1和ISW1在大多数基因上竞争设置间距，CHD1在短间距基因上占优势，ISW1在长间距基因上占优势。相比之下，ISW2只在转录不活跃的基因中起次要作用。大量转录的基因表现出弱相位和极端间隔，要么很短要么很长，并且缺乏连接体组蛋白（H1）。间隔较长的基因在H1中富集，它指导染色质折叠。我们提出CHD1引导短间距，导致H1的排出和染色质展开，而ISW1引导更长的间距，允许H1结合和凝聚染色质。因此，两个重塑子之间为设置每个基因的间距而进行的竞争可能导致高度动态的染色质结构。
Adenosine triphosphate-dependent chromatin remodeling machines play a central role in gene regulation by manipulating chromatin structure. Most genes have a nucleosome-depleted region at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing. We used genome-wide nucleosome sequencing to determine whether these enzymes space nucleosomes differently in vivo. We find that CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing. In contrast, ISW2 plays a minor role, limited to transcriptionally inactive genes. Heavily transcribed genes show weak phasing and extreme spacing, either very short or very long, and are depleted of linker histone (H1). Genes with longer spacing are enriched in H1, which directs chromatin folding. We propose that CHD1 directs short spacing, resulting in eviction of H1 and chromatin unfolding, whereas ISW1 directs longer spacing, allowing H1 to bind and condense the chromatin. Thus, competition between the two remodelers to set the spacing on each gene may result in a highly dynamic chromatin structure.