Department of Biology, Center for Genomics and Systems Biology, New York University, New York 10003.
Department of Biology, Center for Genomics and Systems Biology, New York University, New York 10003
Genetics. 2019 Jul;212(3):729-742. doi: 10.1534/genetics.119.302254. Epub 2019 May 22.
Condensins are evolutionarily conserved protein complexes that are required for chromosome segregation during cell division and genome organization during interphase. In , a specialized condensin, which forms the core of the dosage compensation complex (DCC), binds to and represses chromosome transcription. Here, we analyzed DCC localization and the effect of DCC depletion on histone modifications, transcription factor binding, and gene expression using chromatin immunoprecipitation sequencing and mRNA sequencing. Across the , the DCC accumulates at accessible gene regulatory sites in active chromatin and not heterochromatin. The DCC is required for reducing the levels of activating histone modifications, including H3K4me3 and H3K27ac, but not repressive modification H3K9me3. In -to-autosome fusion chromosomes, DCC spreading into the autosomal sequences locally reduces gene expression, thus establishing a direct link between DCC binding and repression. Together, our results indicate that DCC-mediated transcription repression is associated with a reduction in the activity of chromosomal gene regulatory elements.
凝缩素是进化上保守的蛋白质复合物,对于细胞分裂过程中的染色体分离和细胞间期的基因组组织是必需的。在 中,一种特殊的凝缩素,它形成了剂量补偿复合物(DCC)的核心,与 染色体的转录结合并抑制其转录。在这里,我们使用染色质免疫沉淀测序和 mRNA 测序分析了 DCC 的定位以及 DCC 耗竭对组蛋白修饰、转录因子结合和基因表达的影响。在 中,DCC 聚集在活性染色质而非异染色质的可及性基因调控位点上。DCC 对于降低激活组蛋白修饰的水平是必需的,包括 H3K4me3 和 H3K27ac,但不降低抑制性修饰 H3K9me3。在 X 染色体与常染色体融合的染色体中,DCC 向常染色体序列的扩展局部降低了基因表达,从而在 DCC 结合和抑制之间建立了直接联系。总之,我们的结果表明,DCC 介导的转录抑制与 染色体基因调控元件活性的降低有关。