Gabriel Onea, Alireza Ghahramani, Xu Wang, Haider M Hassan, Nathalie G Bérubé, Caroline Schild-Poulter
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引用次数: 0
摘要
WD-repeat containing protein 26 (WDR26)是CTLH E3连接酶复合物的重要组成部分。WDR26突变导致Skraban-Deardorff,这是一种智力残疾综合征,其临床特征与其他由转录调控和染色质结构缺陷引起的疾病相似。然而,WDR26及其相关的CTLH复合物在调节染色质或转录中的作用尚未阐明。在这里,我们评估了WDR26缺失如何影响染色质可及性和基因表达。WDR26基因敲除的HeLa细胞转录组分析显示有超过2000个差异表达基因,而ATAC-Seq分析显示有超过32000个差异可达的染色质区域,大多数定位于基因间和内含子区域,13% %定位于启动子区域。综上所述,我们发现WDR26缺失影响了AP-1和NF-1转录因子调控基因的表达,并导致其染色质可及性发生巨大变化。总之,我们的分析表明WDR26和CTLH复合物参与染色质调控。
WDR26 depletion alters chromatin accessibility and gene expression profiles in mammalian cells.
WD-repeat containing protein 26 (WDR26) is an essential component of the CTLH E3 ligase complex. Mutations in WDR26 lead to Skraban-Deardorff, an intellectual disability syndrome with clinical features resembling other disorders arising from defects in transcriptional regulation and chromatin structure. However, the role of WDR26 and its associated CTLH complex in regulating chromatin or transcription has not been elucidated. Here, we assessed how loss of WDR26 affects chromatin accessibility and gene expression. Transcriptome analysis of WDR26 knockout HeLa cells revealed over 2000 differentially expressed genes, while ATAC-Seq analysis showed over 32,000 differentially accessible chromatin regions, the majority mapping to intergenic and intronic regions and 13 % mapping to promoters. Above all, we found that WDR26 loss affected expression of genes regulated by AP-1 and NF-1 transcription factors and resulted in dramatic changes in their chromatin accessibility. Overall, our analyses implicate WDR26 and the CTLH complex in chromatin regulation.
期刊介绍:
Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation.
As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.