HMGA1 recruits CTIP2-repressed P-TEFb to the HIV-1 and cellular target promoters

Autor: Houda Hallay, Christian Schwartz, Sebastian Eilebrecht, Valentin Le Douce, Arndt Benecke, Gwenaelle Robette, Raphael Riclet, Carine Van Lint, Olivier Rohr, Brice Targat, Benoît Van Driessche
Přispěvatelé: HAL UPMC, Gestionnaire, Institut des Hautes Etudes Scientifiques (IHES), IHES, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Parasitologie et de Pathologie Tropicale, IUT Louis Pasteur de Schiltigheim, Université libre de Bruxelles (ULB), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut des Hautes Études Scientifiques (IHES)
Rok vydání: 2014
Předmět:
Zdroj: Nucleic Acids Research
Nucleic Acids Research, 2014, 42 (8), pp.4962-4971. ⟨10.1093/nar/gku168⟩
Nucleic Acids Research, Oxford University Press, 2014, 42 (8), pp.4962-4971. ⟨10.1093/nar/gku168⟩
Nucleic acids research, 42 (8
ISSN: 1362-4962
0305-1048
DOI: 10.1093/nar/gku168
Popis: Active positive transcription elongation factor b (P-TEFb) is essential for cellular and human immunodeficiency virus type 1 (HIV-1) transcription elongation. CTIP2 represses P-TEFb activity in a complex containing 7SK RNA and HEXIM1. Recently, the inactive 7SK/P-TEFb small nuclear RNP (snRNP) has been detected at the HIV-1 core promoter as well as at the promoters of cellular genes, but a recruiting mechanism still remains unknown to date. Here we show global synergy between CTIP2 and the 7SK-binding chromatin master-regulator HMGA1 in terms of P-TEFb-dependent endogenous and HIV-1 gene expression regulation. While CTIP2 and HMGA1 concordingly repress the expression of cellular 7SK-dependent P-TEFb targets, the simultaneous knock-down of CTIP2 and HMGA1 also results in a boost in Tat-dependent and independent HIV-1 promoter activity. Chromatin immunoprecipitation experiments reveal a significant loss of CTIP2/7SK/P-TEFb snRNP recruitment to cellular gene promoters and the HIV-1 promoter on HMGA1 knock-down. Our findings not only provide insights into a recruiting mechanism for the inactive 7SK/P-TEFb snRNP, but may also contribute to a better understanding of viral latency. © 2014 © The Author(s) 2014. Published by Oxford University Press.
SCOPUS: ar.j
info:eu-repo/semantics/published
Databáze: OpenAIRE