TRIM24 controls induction of latent HIV-1 by stimulating transcriptional elongation

Abstract Expression of HIV-1 in response to T cell signaling requires TFII-I bound to conserved sites flanking the LTR enhancer. Here we demonstrate that TFII-I recruits tripartite motif protein TRIM24 to the HIV-1 LTR by direct interaction. Constitutive interaction of TRIM24 with the LTR was dependent upon TFII-I, and knockout of TRIM24 impaired reactivation of HIV-1 expression in response to T cell signaling. Loss of TRIM24 did not affect recruitment of RNA Pol II to the LTR promoter, but inhibited transcriptional elongation, an effect associated with decreased RNA Pol II CTD S2 phosphorylation and impaired recruitment of CDK9. Furthermore, TRIM24 deficiency resulted in altered T cell immune response, an effect that is facilitated by TFII-I. These results demonstrate a novel role of TRIM24 for regulation of transcriptional elongation from the HIV-1 promoter, through its interaction with TFII-I, and by recruitment of P-TEFb. Furthermore, these factors co-regulate a significant proportion of genes involved in T cell immune response, consistent with tight coupling of HIV-1 transcriptional activation and T cell signaling.