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Chromatin remodeling is regulated by the ubiquitin proteasome pathway
Author(s) -
Dedes Jennifer,
Li Jun,
BardagGorce Fawzia
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.194
Subject(s) - proteasome , histone deacetylase , histone , chromatin remodeling , histone deacetylase 5 , epigenetics , microbiology and biotechnology , histone methyltransferase , hdac11 , biology , histone acetyltransferase , histone h2a , histone methylation , histone deacetylase 2 , chemistry , gene expression , dna methylation , biochemistry , gene
Nuclear ubiquitin‐proteasome system plays a crucial role in regulating the gene expression, transcription, and DNA repair. Proteasome inhibition causes significant changes in the transcription factors recruitment, and histone modifications. The focus of the present report is to elucidate the mechanism by which the proteasome is regulating the epigenetic phenomenon, and the effect of ethanol feeding on this regulation. Liver gene profiling analysis of rats given proteasome inhibitor, PS341, showed that several genes, such as Gstm2, p53, and Gadd45a and b, were up regulated, and several genes, such as cyclin D1, ADH1, and ALDH, were down regulated. In addition, the expression of histone acetyltransferase p300, MYST, and the histone deacetylase HDAC 4, 5, and 6 were also changed, indicating that histone acetylation changes occurred when the proteasome was inhibited. Histone H2B, which ubiquitination controls histone H3 methylation, was significantly up regulated by proteasome inhibition. In addition, methionine metabolizing enzymes, such as BHMT and MAT1a, were significantly down regulated, suggesting a low level of the methyl donor SAMe production. This study reflects the critical role of the proteasome in regulating vital pathways in the nucleus, in particular, the epigenetic mechanisms that regulate gene expression and DNA repair. Supported by NIH/NIAAA grant 8116.