WDR26 depletion alters chromatin accessibility and gene expression profiles in mammalian cells.

Abstract

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.