Transcription regulation by histone deacetylases.
Dynamic changes in the post-translational modification pattern of histories such as acetylation, deacetylation, phosphorylation, methylation and ubiquitination are thought to provide a code for correct regulation of gene expression by affecting chromatin structure and interaction with regulatory factors. Our studies focus on the role of histone deacetylases (HDACs) in transcriptional regulation and addressing functional differences of class I and class II HDACs. To identify genes that were transcriptionally regulated by specific HDACs, genome scale expression profiles were performed in cancer cells following the inhibition of three HDAC family members by specific oligonucleotides. The modulated genes identified in this study represented a wide range of modifications in different cellular pathways. In addition, treatment of cancer cells with a HDAC inhibitor was found to induce the expression of the small GTPase RhoB through an inverted CCAAT box in the RhoB promoter. These studies identified a specific transcription element involved in HDAC-mediated gene transcription and genes that are transcriptionally regulated by specific HDACs, providing important insight into the potential therapeutic benefit of HDAC inhibition.
Wang
Shaowen
S
Novartis Institutes for Biomedical Research, Inc, 100 Technology Square, Cambridge, MA 02139, USA.
Yan-Neale
Yan
Y
Zeremski
Marija
M
Cohen
Dalia
D
D023081:CCAAT-Binding Factor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000494:pharmacology; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured; D020743:rhoB GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics
D023081:CCAAT-Binding Factor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D010455:Peptides; C067070:trapoxin A; D006655:Histone Deacetylases; D020743:rhoB GTP-Binding Protein