The histone acetyltransferase activity of PCAF cooperates with the brahma/SW12-related protein BRG-1 in the activation of the enhancer A of the MHC class I promoter

Major histocompatibility complex (MHC) class I proteins are an essential co mponent of the immune system allowing the organism to protect from viral in fections and neoplastic transformation. Expression of the MHC class I genes is regulated by a variety of cis-regulatory promoter elements among which the enhancer A is of particular importance. This enhancer is synergisticall y activated through AP-1/ATF and NF-kappaB transcription factors. NF-kappaB recruits the histone acetyltransferase (HAT) p300/CREB-binding protein (CB P) to the multiprotein complex bound to the enhancer A. Here we present evi dence that acetylation and deacetylation processes are involved in the acti vation of the enhancer A. The p300/CBP associated factor PCAF, but not p300 /CBP, counteracts the repression of the enhancer A mediated by the histone deacetylase HDAC1. Furthermore, overexpression of PCAF results in an increa se in the acetylation of histone H4 bound to the enhancer A and HDAC1 count eracts the PCAF-mediated H4 acetylation. The activation function of PCAF re quires the p300/CBP binding motif indicating that PCAF might be recruited t o the enhancer A through an association with p300/CBP. Moreover, PCAF and t he Brahma/SWI2-related protein BRG-1, which is a key factor of the human AT P-dependent chromatin remodelling complex SWI/SNF, synergistically up-regul ate the enhancer A. Synergistic activation requires the HAT domain of PCAF. Taken together our data suggest that members of two different groups of ch romatin modifying complexes are involved in the activation of the enhancer A of the MHC class I promoter. (C) 2001 Elsevier Science B.V. All rights re served.