Histone acetylation is not an accurate predictor of gene expression following treatment with histone deacetylase inhibitors.
Histone deacetylase (HDAC) inhibitors (HDIs) are documented for their role in activation and/or repression of gene expression. Currently, it is believed that HDAC inhibitors act at the histone level to alter chromatin dynamics through the inactivation of HDACs thereby resulting in histone hyperacetylation and increased transcriptional activation. However, transcriptional repression of gene expression is not explained by this model. Indeed, changes in the acetylation status of discreet lysine residues of histones associated with genes repressed by HDAC inhibitors have not been reported. Therefore, we carried out a systematic investigation of the changes in histone acetylation status at the promoter regions of two genes differentially affected by HDIs to gain a better understanding of how changes in histone acetylation correspond to changes in transcriptional activity.
Ellis
D J P
DJ
Department of Biochemistry, The University of Saskatchewan, Saskatchewan Cancer Agency, 20 Campus Dr., Saskatoon, Sask., Canada S7N 4H4.
Lawman
Z K
ZK
Bonham
K
K
D000107:Acetylation / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
C493956:CDKN1A protein, human; D002843:Chromatin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D016392:Proto-Oncogene Proteins pp60(c-src); D008239:Lysine