title: TRIM28 regulates RNA polymerase II promoter-proximal pausing and pause release.
abstract: Promoter-proximal pausing of RNA polymerase II (Pol II) is a major checkpoint in transcription. An unbiased search for new human proteins that could regulate paused Pol II at the HSPA1B gene identified TRIM28. In vitro analyses indicated HSF1-dependent attenuation of Pol II pausing upon TRIM28 depletion, whereas in vivo data revealed de novo expression of HSPA1B and other known genes regulated by paused Pol II upon TRIM28 knockdown. These results were supported by genome-wide ChIP-sequencing analyses of Pol II occupancy that revealed a global role for TRIM28 in regulating Pol II pausing and pause release. Furthermore, in vivo and in vitro mechanistic studies suggest that transcription-coupled phosphorylation regulates Pol II pause release by TRIM28. Collectively, our findings identify TRIM28 as a new factor that modulates Pol II pausing and transcriptional elongation at a large number of mammalian genes.
authors.affiliation: Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Heeyoun
authors.identifier: 0000000300381985
authors.initials: H
authors.lastname: Bunch
authors.affiliation: 1] Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. [2].
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zheng
authors.affiliation: 1] Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA. [2].
authors.forename: Adam
authors.initials: A
authors.lastname: Burkholder
authors.affiliation: 1] Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. [2] Genomics and Proteomics Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Simon T
authors.initials: ST
authors.lastname: Dillon
authors.affiliation: BioMicro Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Shmulik
authors.initials: S
authors.lastname: Motola
authors.affiliation: 1] Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Birrane
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, Boulder, Colorado, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Ebmeier
authors.affiliation: BioMicro Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Levine
authors.affiliation: Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: David
authors.initials: D
authors.lastname: Fargo
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Chemistry and Biochemistry, University of Colorado, Boulder, Boulder, Colorado, USA.
authors.forename: Dylan J
authors.initials: DJ
authors.lastname: Taatjes
authors.affiliation: Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Stuart K
authors.identifier: 0000000199663354
authors.initials: SK
authors.lastname: Calderwood
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D051747:DNA-Activated Protein Kinase / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006801:Humans; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012319:RNA Polymerase II / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; C525621:HSPA1B protein, human; D000076249:Heat Shock Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; D012319:RNA Polymerase II