CBP/p300 lysine acetyltransferases inhibit HIV-1 expression in latently infected T cells.

ABSTRACT: HIV-1 latency is regulated by chromatin modifying enzymes, and histone deacetylase inhibitors (HDACi) cause reactivation of provirus expression. Surprisingly, we observed that inhibitors of the CBP/p300 acetyltransferases also cause reversal of latency in T cells. CBP/p300 inhibitors synergize with various latency reversing agents to cause HIV-1 reactivation. In contrast, inhibition of CBP/p300 impaired reversal of latency by the HDACi SAHA, indicating that CBP/p300 must contribute to acetylation on the HIV-1 LTR associated with HDACi-mediated latency reversal. CBP/p300 inhibition caused loss of H3K27ac and H3K4me3 from the LTR, but did not affect association of the inhibitor protein BRD4. Furthermore, inhibition of the additional lysine acetyltransferases PCAF/GCN5 or KAT6A/KAT6B also cau

SUBMITTER: Horvath RM 

PROVIDER: S-EPMC11617383 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature