Coordination of a Transcriptional Switch by HMGI(Y) Acetylation

Abstract

Dynamic control of interferon-beta (IFN-beta) gene expression requires the regulated assembly and disassembly of the enhanceosome, a higher-order nucleoprotein complex formed in response to virus infection. The enhanceosome activates transcription by recruiting the histone acetyltransferase proteins CREB binding protein (CBP) and p300/CBP-associated factors (PCAF)/GCN5, which, in addition to modifying histones, acetylate HMGI(Y), the architectural component required for enhanceosome assembly. We show that the accurate execution of the IFN-beta transcriptional switch depends on the ordered acetylation of the high-mobility group I protein HMGI(Y) by PCAF/GCN5 and CBP, which acetylate HMGI(Y) at distinct lysine residues on endogenous promoters. Whereas acetylation of HMGI(Y) by CBP at lysine-65 destabilizes the enhanceosome, acetylation of HMGI(Y) by PCAF/GCN5 at lysine-71 potentiates transcription by stabilizing the enhanceosome and preventing acetylation by CBP.

PCAF is a coactivator for p73-mediated transactivation

“…PCAF is a coactivator that enhances the activity of numerous other activators and proteins involved in transcription, including class II transactivator (CIITA) (Spilianakis et al, 2000;Harton et al, 2001), MyoD (Sartorelli et al, 1999;Polesskaya et al, 2000), E2F1 (Martinez-Balbas et al, 2000), TAL1/SCL (Huang et al, 2000), RXR-RAR nuclear receptors (Blanco et al, 1998), E1A (Zhang et al, 2000) and TAF (Muth et al, 2001) and the architectural protein HMGI(Y) (Munshi et al, 2001). PCAF can function alone or together with p300/CBP coactivators through their interaction depending on target promoters.…”

Transcriptional regulation via the NF-κB signaling module

“…However, in mammalian cells, recruitment of NF-kB is often temporally dissociated from recruitment of cooperating transcription factors. For example, the assembly of the b-interferon enhanceosome occurs in a cooperative manner in vitro but in a progressive, stepwise manner in vivo (Munshi et al, 2001). Similarly, on the MIP-2 gene promoter, NF-kB recruitment parallels its nuclear localization dynamics, whereas activator protein-1 recruitment shows a progressive increase over time and remains bound between two pulses of NF-kB recruitment (Bosisio et al, 2006).…”

Transcriptional Regulation by the Acetylation of Nonhistone Proteins in Humans – A New Target for Therapeutics

“…The enhanceosome also interacts with p300/CBP. p300/CBP as well as PCAF acetylate HMGA (43). Acetylation of HMGA by p300 and CBP induces the disruption of enhanceosome.…”