Runx1 binds positive transcription elongation factor b and represses transcriptional elongation by RNA polymerase II: possible mechanism of CD4 silencing.
Runx1 binds the silencer and represses CD4 transcription in immature thymocytes. In this study, we found that Runx1 inhibits P-TEFb, which contains CycT1, CycT2, or CycK and Cdk9 and stimulates transcriptional elongation by RNA polymerase II (RNAPII) in eukaryotic cells. Indeed, its inhibitory domain, spanning positions 371 to 411, not only bound CycT1 but was required for silencing CD4 transcription in vivo. Our chromatin immunoprecipitation assays revealed that Runx1 inhibits the elongation but not initiation of transcription and that RNAPII is engaged at the CD4 promoter but is unable to elongate in CD4(-) CD8(+) thymoma cells. These results suggest that active repression by Runx1 occurs by blocking the elongation by RNAPII, which may contribute to CD4 silencing during T-cell development.
Jiang
Huimin
H
Department of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, 94143-0703, USA.
Zhang
Fan
F
Kurosu
Takeshi
T
Peterlin
B Matija
BM
D015704:CD4 Antigens / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D056906:Cyclin T; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D042925:Positive Transcriptional Elongation Factor B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013945:Thymoma; D014158:Transcription, Genetic
C113028:CCNK protein, human; C503684:CCNT1 protein, human; C441622:CCNT2 protein, human; D015704:CD4 Antigens; D050676:Core Binding Factor Alpha 2 Subunit; D056906:Cyclin T; D016213:Cyclins; C493728:RUNX1 protein, human; D042925:Positive Transcriptional Elongation Factor B; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D012319:RNA Polymerase II