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Virology. 2003 Feb 1;306(1):68-76.

Chromatin repression by COUP-TFII and HDAC dominates activation by NF-kappaB in regulating major histocompatibility complex class I transcription in adenovirus tumorigenic cells.

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1
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

In adenovirus type 12 transformed cells, the down-regulation of MHC class I transcription contributes to the tumorigenic phenotype and is solely mediated by Ad12 E1A. Previous in vitro studies with class I enhancer sequences have indicated that there is an increased binding of repressor COUP-TFII and its associated HDAC and a decreased binding of activator NF-kappaB. In this study, we used chromatin immunoprecipitation (ChIP) assay in order to determine in vivo whether these proteins regulate class I transcription by affecting chromatin. The ChIP assay revealed that there is lack of chromatin histone acetylation in the region of the class I enhancer in Ad12-transformed cells. This is regulated by histone deacetylation as it was further demonstrated in vivo that COUP-TFII and HDAC are associated with the class I enhancer chromatin. In agreement with in vitro studies, NF-kappaB could be recruited to the class I enhancer following induction by TNF-alpha. However, this enhancer-bound NF-kappaB failed to up-regulate class I expression because the class I enhancer chromatin remained repressed as a result of histone deacetylation by HDAC in association with COUP-TFII. Thus, we have demonstrated for the first time that repression of chromatin through histone deacetylation is a major mechanism in down-regulating class I transcription in Ad12-transformed cells. Finally, Ad12 E1A, a non-DNA binding protein, was shown to be present in the natural protein complex bound to the class I enhancer.

PMID:
12620799
[Indexed for MEDLINE]
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