{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen X"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","NCI NIH HHS","NIAMS NIH HHS","NIGMS NIH HHS"],"pagination":["eadq5091"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11756345"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(774)"],"pubmed_abstract":["Macrophages are key drivers of inflammation and tissue damage in autoimmune diseases including rheumatoid arthritis. The rate-limiting step for transcription of more than 70% of inducible genes in macrophages is RNA polymerase II (Pol II) promoter-proximal pause release; however, the specific role of Pol II early elongation control in inflammation, and whether it can be modulated therapeutically, is unknown. Genetic ablation of a pause-stabilizing negative elongation factor (NELF) in macrophages did not affect baseline Pol II occupancy but enhanced the transcriptional response of paused anti-inflammatory genes to lipopolysaccharide followed by secondary attenuation of inflammatory signaling in vitro and in the K/BxN serum transfer mouse model of arthritis. To pharmacologically disrupt the "],"journal":["Science translational medicine"],"pubmed_title":["Disrupting the RNA polymerase II transcription cycle through CDK7 inhibition ameliorates inflammatory arthritis."],"pmcid":["PMC11756345"],"funding_grant_id":["R01 AI148129","R01 CA258553","R01 AI148435","UC2 AR081025","R35 GM127289","R01 DK099087"],"pubmed_authors":["Deochand DK","Fisher RP","Soussana TN","Rogatsky I","Ramirez DC","Zhang T","Gray NS","Mantel I","Fisher L","Bell RD","Donlin LT","Goodman SM","Chinenov Y","Chen X","Shibu G","Sokolsky BA","Dacic M"],"additional_accession":[]},"is_claimable":false,"name":"Disrupting the RNA polymerase II transcription cycle through CDK7 inhibition ameliorates inflammatory arthritis.","description":"Macrophages are key drivers of inflammation and tissue damage in autoimmune diseases including rheumatoid arthritis. The rate-limiting step for transcription of more than 70% of inducible genes in macrophages is RNA polymerase II (Pol II) promoter-proximal pause release; however, the specific role of Pol II early elongation control in inflammation, and whether it can be modulated therapeutically, is unknown. Genetic ablation of a pause-stabilizing negative elongation factor (NELF) in macrophages did not affect baseline Pol II occupancy but enhanced the transcriptional response of paused anti-inflammatory genes to lipopolysaccharide followed by secondary attenuation of inflammatory signaling in vitro and in the K/BxN serum transfer mouse model of arthritis. To pharmacologically disrupt the ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-06-11T04:53:37.812Z","creation":"2026-06-11T03:07:55.434Z"},"accession":"S-EPMC11756345","cross_references":{"pubmed":["39565872"],"doi":["10.1126/scitranslmed.adq5091"]}}