SNFing HIV transcription

Abstract

The SWI/SNF chromatin remodeling complex is an essential regulator of transcription of cellular genes. HIV-1 infection induces exit of a core component of SWI/SNF, Ini1, into the cytoplasm and its association with the viral pre-integration complex. Several recent papers published in EMBO Journal, Journal of Biological Chemistry, and Retrovirology provide new information regarding possible functions of Ini1 and SWI/SNF in HIV life cycle. It appears that Ini1 has an inhibitory effect on pre-integration steps of HIV replication, but also contributes to stimulation of Tat-mediated transcription. This stimulation involves displacement of the nucleosome positioned at the HIV promoter.

Figure 1

A model depicting mechanisms of Nuc-1 remodeling during HIV-1 transcription. +1 denotes the transcription start site in the HIV-1 LTR. Basal HIV promoter shows an elongation defect due to deficient loading of the transcriptional elongation complex pTEFb. Tat binding to the TAR stem-loop in the nascent viral RNA recruits pTEFb, which phosphorylates the C-terminal domain of RNA pol II and increases transcriptional elongation. Via interaction with the BRM, a catalytic subunit of SWI/SNF complexes, and a core subunit Ini1/SNF5, Tat also recruits the SWI/SNF complex, which initiates remodeling of nuc-1. Subsequent acetylation of the Tat lysine 50 by p300 results in Tat dissociation from TAR, but creates the binding sites for another SWI/SNF catalytic subunit, BRG1. The SWI/SNF complex recruited by the Tat acetylated on lysine 50 (which may be different from the one recruited by the TAR-bound Tat) completes remodeling of nuc-1 and allows the efficient elongation of transcription. See text for details.