The histone acetyltransferase activity of PCAF cooperates with the brahma/SWI2-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 component of the immune system allowing the organism to protect from viral infections 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 synergistically activated through AP-1/ATF and NF-kappa B transcription factors. NF-kappa B recruits the histone acetyltransferase (HAT) p300/CREB-binding protein (CBP) to the multiprotein complex bound to the enhancer A. Here we present evidence that acetylation and deacetylation processes are involved in the activation 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 increase in the acetylation of histone H4 bound to the enhancer A and HDAC1 counteracts the PCAF-mediated H4 acetylation. The activation function of PCAF requires the p300/CBP binding motif indicating that PCAF might be recruited to the enhancer A through an association with p300/CBP. Moreover, PCAF and the Brahma/SWI2-related protein BRG-1, which is a key factor of the human ATP-dependent chromatin remodelling complex SWI/SNF, synergistically up-regulate the enhancer A. Synergistic activation requires the HAT domain of PCAF. Taken together our data suggest that members of two different groups of chromatin modifying complexes are involved in the activation of the enhancer A of the MHC class I promoter.
Brockmann
D
D
Institute of Molecular Biology (Cancer Research), University of Essen Medical School, Hufelandstrasse 55, 45122 Essen, Germany. dieter.brockmann@uni-essen.de
Lehmkühler
O
O
Schmücker
U
U
Esche
H
H
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I / Q000235:genetics*; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D015500:Chloramphenicol O-Acetyltransferase; D004265:DNA Helicases; D051548:Histone Acetyltransferases; D006657:Histones; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C084108:SMARCA4 protein, human