{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Szczepanski A"],"funding":["American Cancer Society","U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences","NIAID NIH HHS","NHLBI NIH HHS","U.S. Department of Defense","NHGRI NIH HHS","U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute","NIGMS NIH HHS"],"pagination":["2067"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10920751"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Recent studies have identified a previously uncharacterized protein C11orf53 (now named POU2AF2/OCA-T1), which functions as a robust co-activator of POU2F3, the master transcription factor which is critical for both normal and neoplastic tuft cell identity and viability. Here, we demonstrate that POU2AF2 dictates opposing transcriptional regulation at distal enhance elements. Loss of POU2AF2 leads to an inhibition of active enhancer nearby genes, such as tuft cell identity genes, and a derepression of Polycomb-dependent poised enhancer nearby genes, which are critical for cell viability and differentiation. Mechanistically, depletion of POU2AF2 results in a global redistribution of the chromatin occupancy of the SWI/SNF complex, leading to a significant 3D genome structure change and a subsequent transcriptional reprogramming. Our genome-wide CRISPR screen further demonstrates that POU2AF2 depletion or SWI/SNF inhibition leads to a PTEN-dependent cell growth defect, highlighting a potential role of POU2AF2-SWI/SNF axis in small cell lung cancer (SCLC) pathogenesis. Additionally, pharmacological inhibition of SWI/SNF phenocopies POU2AF2 depletion in terms of gene expression alteration and cell viability decrease in SCLC-P subtype cells. Therefore, impeding POU2AF2-mediated transcriptional regulation represents a potential therapeutic approach for human SCLC therapy."],"journal":["Nature communications"],"pubmed_title":["A SWI/SNF-dependent transcriptional regulation mediated by POU2AF2/C11orf53 at enhancer."],"pmcid":["PMC10920751"],"funding_grant_id":["R01 HL153122","R35 GM146979","R01 HL149883","R01 HG009906","R35GM124820","P01 HL154998","U19 AI135964","R01HG009906","RSG-22-039-01-DMC","R01 HG011207","R35 GM124820","R01HG011207","HT94252310360"],"pubmed_authors":["Wang P","Zhang T","Yue F","Tsuboyama N","Lyu H","Singer BD","Szczepanski A","Zhao Z","Beytullahoglu O","Wang L"],"additional_accession":[]},"is_claimable":false,"name":"A SWI/SNF-dependent transcriptional regulation mediated by POU2AF2/C11orf53 at enhancer.","description":"Recent studies have identified a previously uncharacterized protein C11orf53 (now named POU2AF2/OCA-T1), which functions as a robust co-activator of POU2F3, the master transcription factor which is critical for both normal and neoplastic tuft cell identity and viability. Here, we demonstrate that POU2AF2 dictates opposing transcriptional regulation at distal enhance elements. Loss of POU2AF2 leads to an inhibition of active enhancer nearby genes, such as tuft cell identity genes, and a derepression of Polycomb-dependent poised enhancer nearby genes, which are critical for cell viability and differentiation. Mechanistically, depletion of POU2AF2 results in a global redistribution of the chromatin occupancy of the SWI/SNF complex, leading to a significant 3D genome structure change and a subsequent transcriptional reprogramming. Our genome-wide CRISPR screen further demonstrates that POU2AF2 depletion or SWI/SNF inhibition leads to a PTEN-dependent cell growth defect, highlighting a potential role of POU2AF2-SWI/SNF axis in small cell lung cancer (SCLC) pathogenesis. Additionally, pharmacological inhibition of SWI/SNF phenocopies POU2AF2 depletion in terms of gene expression alteration and cell viability decrease in SCLC-P subtype cells. Therefore, impeding POU2AF2-mediated transcriptional regulation represents a potential therapeutic approach for human SCLC therapy.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-07-05T03:16:16.949Z","creation":"2026-07-05T03:11:26.168Z"},"accession":"S-EPMC10920751","cross_references":{"pubmed":["38453939"],"doi":["10.1038/s41467-024-46492-5"]}}