Requirement for SWI/SNF chromatin-remodeling complex in Tat-mediated activation of the HIV-1 promoter

Abstract

Activation of the human immunodeficiency virus type-1 (HIV-1) promoter in infected cells requires the sequential recruitment of several cellular factors to facilitate the formation of a processive elongation complex. The nucleosomal reorganization of the HIV-1 long terminal repeat (LTR) observed upon Tat stimulation suggests that chromatin-remodeling complexes could play a role during this process. Here, we reported that Tat interacts directly with Brm, a DNA-dependent ATPase subunit of the SWI/SNF chromatin-remodeling complex, to activate the HIV-1 LTR. Inhibition of Brm via small interfering RNAs impaired Tatmediated transactivation of an integrated HIV-1 promoter. Furthermore, Brm is recruited in vivo to the HIV-1 LTR in a Tat-dependent manner. Interestingly, we found that Tat/ Brm interaction is regulated by Tat lysine 50 acetylation. These data show the requirement of Tat-mediated recruitment of SWI/SNF chromatin-remodeling complex to HIV-1 promoter in the activation of the LTR.

von Hippel–Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step

“…To test whether the effect of VBP1 depends on integrasedependent or -independent integration, we used distinct clones stably transfected with luciferase gene under the control of HIV-1 promoter and measured the Tat-induced transcription of luciferase gene (36). Luciferase or cyclin T1-targeted siRNAs strongly inhibited luciferase expression, whereas silencing VBP1 but also pVHL in these cells had no major effect on Tatmediated transactivation of the integrated HIV-1 promoter per se (Fig.…”

The Werner Syndrome Helicase Is a Cofactor for HIV-1 Long Terminal Repeat Transactivation and Retroviral Replication

“…The mechanism by which Tat/TAR-RNA complexes regulate transcription from the HIV-1 LTR involves the concerted recruitment of a plethora of cellular factors, including p300/CREB-binding protein (p300/CBP) (18 -25), PCAF/hGCN5 (20 -22, 26 -30), P-TEFb (30 -33), SET7/SET9 methyltransferases (34), SIRT1 (35), the Brm component of the SWI/SNF chromatin-remodeling com-plex (36), and the splicing factor, SKIP (37). The Tat protein is acetylated on Lys 28 , Lys 50 , and Lys 51 by the transcriptional coactivators/acetyltransferases, p300/CBP and PCAF/hGCN5 (20 -22, 24, 27-30, 38), which has been shown to modulate Tat interactions with P-TEFb and Brm, as well as the ability of Tat for binding TAR-RNA (20,30,35,36,39). The formation of Tat/TAR-RNA/P-TEFb/PCAF complexes on the HIV-1 LTR stimulates Ser 2 -Ser 5 -phosphorylation of the RNA pol II carboxyl-terminal domain associated with increased transcriptional elongation (30,37,40).…”

The Regulation of HIV-1 mRNA Biogenesis

“…Lysines at positions 50 and 51 are major substrates for acetylation by p300 and hGCN5 (Col, et al, 2001, Deng, et al, 2001, Kiernan, et al, 1999. Acetylation of lysine 50 of Tat promotes the dissociation of Tat from TAR RNA during early transcription elongation and recruitment of the SWI/SNF chromatin-remodeling complex (Treand, et al, 2006), which synergize with p300 acetyltransferase and acetylated Tat to remodel the nucleosome at the HIV promoter in order to activate transcription (Mahmoudi, et al, 2006). Furthermore, acetylation of lysine 50 triggers the recruitment of P/CAF to the elongating RNA Pol II (Dorr, et al, 2002).…”