P-TEFb Kinase Complex Phosphorylates Histone H1 to Regulate Expression of Cellular and HIV-1 Genes

• Published in: The Journal of biological chemistry Vol. 285; no. 39; pp. 29713 - 29720
• Main Authors: O'Brien, Siobhan K., Cao, Hong, Nathans, Robin, Ali, Akbar, Rana, Tariq M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.09.2010; American Society for Biochemistry and Molecular Biology
• Subjects: Cyclin T - genetics; Cyclin T - metabolism; Cyclin-Dependent Kinase 9 - genetics; Cyclin-Dependent Kinase 9 - metabolism; DNA and Chromosomes; Flavonoids - pharmacology; Gene Expression Regulation, Viral - drug effects; Gene Expression Regulation, Viral - physiology; Gene Regulation; Genes, Viral - physiology; HeLa Cells; Histone Modification; Histones; Histones - genetics; Histones - metabolism; HIV; HIV Infections - genetics; HIV Infections - metabolism; HIV-1 - genetics; HIV-1 - metabolism; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - metabolism; Human immunodeficiency virus 1; Humans; Multienzyme Complexes - genetics; Multienzyme Complexes - metabolism; Phosphorylation - drug effects; Phosphorylation - genetics; Piperidines - pharmacology; Positive Transcriptional Elongation Factor B - genetics; Positive Transcriptional Elongation Factor B - metabolism; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; RNA Polymerase II; tat Gene Products, Human Immunodeficiency Virus - genetics; tat Gene Products, Human Immunodeficiency Virus - metabolism; Transcription Regulation; Histones; Transcription Regulation; Histone Modification; HIV; RNA Polymerase II
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.125997

Transcription of HIV-1 genes depends on the RNA polymerase II kinase and elongation factor positive transcription elongation factor b (P-TEFb), the complex of cyclin T1 and CDK9. Recent evidence suggests that regulation of transcription by P-TEFb involves chromatin binding and modifying factors. To determine how P-TEFb may connect chromatin remodeling to transcription, we investigated the relationship between P-TEFb and histone H1. We identify histone H1 as a substrate for P-TEFb involved in cellular and HIV-1 transcription. We show that P-TEFb interacts with H1 and that P-TEFb inhibition by RNAi, flavopiridol, or dominant negative CDK9 expression correlates with loss of phosphorylation and mobility of H1 in vivo. Importantly, P-TEFb directs H1 phosphorylation in response to wild-type HIV-1 infection, but not Tat-mutant HIV-1 infection. Our results show that P-TEFb phosphorylates histone H1 at a specific C-terminal phosphorylation site. Expression of a mutant H1.1 that cannot be phosphorylated by P-TEFb also disrupts Tat transactivation in an HIV reporter cell line as well as transcription of the c-fos and hsp70 genes in HeLa cells. We identify histone H1 as a novel P-TEFb substrate, and our results suggest new roles for P-TEFb in both cellular and HIV-1 transcription.