Similar Datasets
Project description: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-null 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.
2025-01-21 | GSE273059 | GEO
Project description:Wdr26 is a gene induced during red cell development. In order to understand the function of wdr26 during erythropoiesis, we analyzed the transcriptomes of wild type and Wdr26-knockout mouse eythroleukemia (MEL) cells. We found that loss of Wdr26 did not cause a global increase in the expression of genes that encode nuclear proteins.
2019-09-01 | GSE133287 | GEO
Project description: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-null 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.
2025-01-21 | GSE273060 | GEO
Project description:Selective protein degradation by the Ubiquitin Proteasome System (UPS) is largely regulated by multi-subunit E3 ligase complexes commonly utilizing interchangeable degron-receptors to target a plethora of different substrates. Here, we identified nicotinamide/nicotinacid-mononlucletide-adenylyltransferase 1 (NMNAT1) as a cognate substrate of CTLH E3 complex, and report structural, biochemical, and cell biology studies revealing a mechanism of a degron-selective receptor function of the inherent non-interchangeable CTLH supramolecular assembly subunit WDR26, tailored to avidly bind and target NMNAT1 hexamer. Importantly, WDR26 receptor is gated by a degron-mimicry of the N-terminus of the CTLH subunit YPEL5 that corrupts ubiquitin targeting of NMNAT1. Cellular YPEL5 depletion is sufficient to destabilize NMNAT1 and to attenuate cytotoxicity of the NMNAT1-activated anticancer drug Tiazofurin. Cumulatively, we propose a regulatory concept of degron selection and binding by the WDR26-CTLH supramolecular assembly, potentially applying to substrates other than NMNAT1.
2024-05-16 | PXD044126 | Pride