{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hyder U"],"funding":["U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)","NIDDK NIH HHS","NIAID NIH HHS","U.S. Department of Health & Human Services | NIH | National Cancer Institute","NCI NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)","Cecil H. and Ida Green Center for Reproductive Biology Sciences Endowment","U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["5859"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11245487"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Signal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction remain poorly understood. By combining an acute depletion system with several genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Acute KAP1 loss triggers an increase in RNA polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation thereby dampening IEGs transcriptional output. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions."],"journal":["Nature communications"],"pubmed_title":["KAP1 negatively regulates RNA polymerase II elongation kinetics to activate signal-induced transcription."],"pmcid":["PMC11245487"],"funding_grant_id":["R01 AI114362","P50 CA196516","P50 CA070907","R01 DK058110","F99CA264296","R03 CA259672","R01DK058110","F99 CA264296","P30 CA142543"],"pubmed_authors":["Thornton M","D'Orso I","Challa A","Kraus WL","Nandu T","Hyder U"],"additional_accession":[]},"is_claimable":false,"name":"KAP1 negatively regulates RNA polymerase II elongation kinetics to activate signal-induced transcription.","description":"Signal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction remain poorly understood. By combining an acute depletion system with several genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Acute KAP1 loss triggers an increase in RNA polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation thereby dampening IEGs transcriptional output. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2025-04-18T21:43:08.801Z","creation":"2025-02-19T02:33:53.331Z"},"accession":"S-EPMC11245487","cross_references":{"pubmed":["38997286"],"doi":["10.1038/s41467-024-49905-7"]}}