Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression in Dictyostelium.
Regulation of nucleosome positioning by a CHD Type III chromatin remodeler and its relationship to developmental gene expression in Dictyostelium.
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DOI：
10.1101/gr.216309.116
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发表时间：
2017-04
期刊：
影响因子：
7
通讯作者：
Harwood AJ
中科院分区：
文献类型：
--
作者：
Platt JL;Kent NA;Kimmel AR;Harwood AJ
核小体的放置和重新定位可以指导单个基因的转录;然而，这些事件的精确相互作用是复杂的，并且在全基因组水平上很大程度上未得到解决。染色体结构域-解旋酶-DNA结合（CHD）III型蛋白是控制核小体定位的SWI 2/SNF 2蛋白的亚家族，并且与几种复杂的人类疾病（包括CHARGE综合征和自闭症）相关。III型CHD是动物和网骨藻的多细胞发育所必需的，但在植物和酵母中不存在。这些CHDs在体外可介导核小体易位，但其体内机制尚不清楚。在这里，我们使用核小体定位和转录谱的全基因组分析，以调查在野生型（WT）Dictyosteopathy和缺乏ChdC，III型CHD蛋白直系同源物的突变细胞的发展过程中核小体定位和基因表达之间的体内关系。我们证明了与WT发育基因调控相关的主要核小体位置变化。chdC的缺失导致基因内核小体间距的增加和基因表达的失调，影响WT发育过程中重新定位的基因的约50%。这些分析表明，活跃的核小体重新定位在Dictyosteoblasts多细胞发育，建立CHD III型染色质重塑蛋白在这个过程中的体内功能，并揭示了详细的核小体定位和基因调控之间的关系，细胞之间的发展状态的转变。
Nucleosome placement and repositioning can direct transcription of individual genes; however, the precise interactions of these events are complex and largely unresolved at the whole-genome level. The Chromodomain-Helicase-DNA binding (CHD) Type III proteins are a subfamily of SWI2/SNF2 proteins that control nucleosome positioning and are associated with several complex human disorders, including CHARGE syndrome and autism. Type III CHDs are required for multicellular development of animals and Dictyostelium but are absent in plants and yeast. These CHDs can mediate nucleosome translocation in vitro, but their in vivo mechanism is unknown. Here, we use genome-wide analysis of nucleosome positioning and transcription profiling to investigate the in vivo relationship between nucleosome positioning and gene expression during development of wild-type (WT) Dictyostelium and mutant cells lacking ChdC, a Type III CHD protein ortholog. We demonstrate major nucleosome positional changes associated with developmental gene regulation in WT. Loss of chdC caused an increase of intragenic nucleosome spacing and misregulation of gene expression, affecting ∼50% of the genes that are repositioned during WT development. These analyses demonstrate active nucleosome repositioning during Dictyostelium multicellular development, establish an in vivo function of CHD Type III chromatin remodeling proteins in this process, and reveal the detailed relationship between nucleosome positioning and gene regulation, as cells transition between developmental states.