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P-TEFb kinase complex phosphorylates histone H1 to regulate expression of cellular and HIV-1 genes.

Abstract
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.
AuthorsSiobhan K O'Brien, Hong Cao, Robin Nathans, Akbar Ali, Tariq M Rana
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 39 Pg. 29713-20 (Sep 24 2010) ISSN: 1083-351X [Electronic] United States
PMID20551309 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • CCNT1 protein, human
  • Cyclin T
  • Flavonoids
  • HSP70 Heat-Shock Proteins
  • Histones
  • Multienzyme Complexes
  • Piperidines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-fos
  • tat Gene Products, Human Immunodeficiency Virus
  • alvocidib
  • Positive Transcriptional Elongation Factor B
  • CDK9 protein, human
  • Cyclin-Dependent Kinase 9
Topics
  • Cyclin T (genetics, metabolism)
  • Cyclin-Dependent Kinase 9 (genetics, metabolism)
  • Flavonoids (pharmacology)
  • Gene Expression Regulation, Viral (drug effects, physiology)
  • Genes, Viral (physiology)
  • HIV Infections (genetics, metabolism)
  • HIV-1 (genetics, metabolism)
  • HSP70 Heat-Shock Proteins (genetics, metabolism)
  • HeLa Cells
  • Histones (genetics, metabolism)
  • Humans
  • Multienzyme Complexes (genetics, metabolism)
  • Phosphorylation (drug effects, genetics)
  • Piperidines (pharmacology)
  • Positive Transcriptional Elongation Factor B (genetics, metabolism)
  • Protein Kinase Inhibitors (pharmacology)
  • Proto-Oncogene Proteins c-fos (genetics, metabolism)
  • tat Gene Products, Human Immunodeficiency Virus (genetics, metabolism)

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