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.
|
Authors | Siobhan K O'Brien, Hong Cao, Robin Nathans, Akbar Ali, Tariq M Rana |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 285
Issue 39
Pg. 29713-20
(Sep 24 2010)
ISSN: 1083-351X [Electronic] United States |
PMID | 20551309
(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)
|