{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Miao L"],"funding":["Intramural NIH HHS","NCI NIH HHS"],"pagination":["e188924"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12700541"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["135(24)"],"pubmed_abstract":["Over 15% of cancers worldwide are caused by viruses. Merkel cell polyomavirus (MCPyV) is the most recently discovered human oncovirus and is the only polyomavirus that drives malignant tumors in humans. Here, we show that MCPyV+ Merkel cell carcinoma is defined by neuroendocrine-lineage core regulatory (CR) transcription factors (TFs) (ATOH1, INSM1, ISL1, LHX3, POU4F3, and SOX2) that were essential for tumor survival and that co-bound chromatin with the viral small T antigen at super enhancers. Moreover, MCPyV integration sites were enriched at these neuroendocrine super enhancers. We further discovered that the MCPyV noncoding control region contained a homeodomain binding motif absent in other polyomaviruses that bound ISL1 and LHX3 and depended on them for T antigen expression. To thera"],"journal":["The Journal of clinical investigation"],"pubmed_title":["Interlocking host and viral cis-regulatory networks drive Merkel cell carcinoma."],"pmcid":["PMC12700541"],"funding_grant_id":["ZIA AR041222","R01 CA291963"],"pubmed_authors":["Shen M","Gelb T","Alexander T","Milewski D","Garman KA","Miao L","Daily K","Porch J","Choi R","Hall MD","Coxon A","Gangalapudi V","Song Y","Starrett GJ","Sallari R","Morton A","Collado L","Hill NT","Khan J","Khanna A","Vilasi S","Reed D","Vakoc CR","Urban DJ","Gryder BE","Chakraborty M","Seaman J","Busam KJ","Brownell I"],"additional_accession":[]},"is_claimable":false,"name":"Interlocking host and viral cis-regulatory networks drive Merkel cell carcinoma.","description":"Over 15% of cancers worldwide are caused by viruses. Merkel cell polyomavirus (MCPyV) is the most recently discovered human oncovirus and is the only polyomavirus that drives malignant tumors in humans. Here, we show that MCPyV+ Merkel cell carcinoma is defined by neuroendocrine-lineage core regulatory (CR) transcription factors (TFs) (ATOH1, INSM1, ISL1, LHX3, POU4F3, and SOX2) that were essential for tumor survival and that co-bound chromatin with the viral small T antigen at super enhancers. Moreover, MCPyV integration sites were enriched at these neuroendocrine super enhancers. We further discovered that the MCPyV noncoding control region contained a homeodomain binding motif absent in other polyomaviruses that bound ISL1 and LHX3 and depended on them for T antigen expression. To thera","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-15T06:26:15.896Z","creation":"2026-06-15T03:09:11.811Z"},"accession":"S-EPMC12700541","cross_references":{"pubmed":["41392987"],"doi":["10.1172/JCI188924"]}}