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.

Brockmann, D; Lehmkühler, O; Schmücker, U; Esche, H

Brockmann, D; Lehmkühler, O; Schmücker, U; Esche, H.

Afiliación

Brockmann D; Institute of Molecular Biology (Cancer Research), University of Essen Medical School, Hufelandstrasse 55, 45122 Essen, Germany. dieter.brockmann@uni-essen.de

Gene ; 277(1-2): 111-20, 2001 Oct 17.

Article en En | MEDLINE | ID: mdl-11602348

RESUMEN

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.

Asunto(s)

Acetiltransferasas/metabolismo; Proteínas de Ciclo Celular/metabolismo; Elementos de Facilitación Genéticos/genética; Genes MHC Clase I/genética; Proteínas Nucleares/metabolismo; Regiones Promotoras Genéticas/genética; Proteínas de Saccharomyces cerevisiae; Factores de Transcripción/metabolismo; Acetilación; Acetiltransferasas/genética; Western Blotting; Proteínas de Ciclo Celular/genética; Cloranfenicol O-Acetiltransferasa/genética; Cloranfenicol O-Acetiltransferasa/metabolismo; ADN Helicasas; Regulación de la Expresión Génica; Células HeLa; Histona Acetiltransferasas; Histonas/metabolismo; Humanos; Proteínas Nucleares/genética; Plásmidos/genética; Proteínas Recombinantes de Fusión/genética; Proteínas Recombinantes de Fusión/metabolismo; Factores de Transcripción/genética; Transfección; Células Tumorales Cultivadas; Factores de Transcripción p300-CBP

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acetiltransferasas / Factores de Transcripción / Genes MHC Clase I / Proteínas Nucleares / Elementos de Facilitación Genéticos / Regiones Promotoras Genéticas / Proteínas de Ciclo Celular / Proteínas de Saccharomyces cerevisiae Límite: Humans Idioma: En Revista: Gene Año: 2001 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Países Bajos

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