1. HDAC inhibitors prevent the induction of the immediate-early gene FOSL1, but do not alter the nucleosome response
- Author
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Dilshad H. Khan and James R. Davie
- Subjects
Transcriptional Activation ,Biophysics ,Histone Deacetylase 2 ,Histone Deacetylase 1 ,Hydroxamic Acids ,Biochemistry ,Peptides, Cyclic ,Histone Deacetylases ,Mitogen- and stress-activated protein kinase ,03 medical and health sciences ,Histone H3 ,0302 clinical medicine ,Structural Biology ,Genetics ,medicine ,Nucleosome ,Humans ,Histone deacetylase ,Molecular Biology ,Genes, Immediate-Early ,030304 developmental biology ,Immediate-early gene ,0303 health sciences ,biology ,Chemistry ,Cell Biology ,HCT116 Cells ,Chromatin immunoprecipitation ,3. Good health ,Nucleosomes ,Gene Expression Regulation, Neoplastic ,Histone Deacetylase Inhibitors ,Histone H3 phosphorylation ,Trichostatin A ,Histone ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Tetradecanoylphorbol Acetate ,Signal transduction ,Immediate early gene ,Proto-Oncogene Proteins c-fos ,Transcription ,medicine.drug - Abstract
Dynamic histone acetylation, catalyzed by lysine acetyltransferases and HDACs, is critical to IEG expression. Expression of IEGs, such as FOSL1, is induced by several signal transduction pathways resulting in activation of the protein kinase MSK and phosphorylation of histone H3 at serine 10 of nucleosomes (the nucleosome response) at the upstream promoter and regulatory region of target genes. HDAC inhibitors prevent FOSL1 gene induction and the association of HDAC1, 2 and 3 with the gene body. However, HDAC inhibitors did not prevent the nucleosome response. Thus HDAC inhibitors perturb events downstream of the nucleosome response required for FOSL1 transcription initiation.
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