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

Abstract : Active positive transcription elongation factor b (P-TEFb) is essential for cellular and human im-munodeficiency 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.
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Submitted on : Thursday, June 16, 2016 - 11:17:44 AM
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Nucl. Acids Res.-2014-Eilebrec...
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Sebastian Eilebrecht, Valentin Le Douce, Raphael Riclet, Brice Targat, Houda Hallay, et al.. HMGA1 recruits CTIP2-repressed P-TEFb to the HIV-1 and cellular target promoters. Nucleic Acids Research, Oxford University Press, 2014, 42 (8), pp.4962-4971. ⟨10.1093/nar/gku168⟩. ⟨hal-01332585⟩



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