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PMID: 8723390 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation.

Gene expression ·Vol. 5 ·No. 4-5 ·1996-00-00 ·Pages 245-53

Van Lint C, Emiliani S, Verdin E

Abstract

Posttranslational modifications of histones in chromatin are emerging as an important mechanism in the regulation of gene expression. Changes in histone acetylation levels occur during many nuclear processes such as replication, transcriptional silencing, and activation. Histone acetylation levels represent the result of a dynamic equilibrium between competing histone deacetylase(s) and histone acetylase(s). We have used two new specific inhibitors of histone deacetylase, trichostatin A (TSA) and trapoxin (TPX), to probe the effect of histone hyperacetylation on gene expression. We confirm that both drugs block histone deacetylase activity and have no detectable effects on histone acetylation rates in human lymphoid cell lines. Treatment with either TSA or TPX results in the transcriptional activation of HIV-1 gene expression in latently infected cell lines. In contrast, TSA and TPX cause a rapid decrease in c-myc gene expression and no change in the expression of the gene for glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Using differential display to compare the differences in gene expression between untreated cells and cells treated with TSA, we found that the expression of approximately 2% of cellular genes (8 genes out of approximately 340 examined) changes in response to TSA treatment. These results demonstrate that the transcriptional regulation of a restricted set of cellular genes is uniquely sensitive to the degree of histone acetylation in chromatin.

MeSH Terms
Acetylation Anti-Bacterial Agents/pharmacology Cell Line Chromatin/chemistry,genetics,metabolism Enzyme Inhibitors/pharmacology Gene Expression Regulation/drug effects Genes, Viral/drug effects Genes, myc/drug effects HIV-1/genetics Histone Deacetylase Inhibitors Histone Deacetylases/metabolism Histones/chemistry,metabolism Humans Hydroxamic Acids/pharmacology Peptides Protein Processing, Post-Translational
Chemicals
Anti-Bacterial Agents Chromatin Enzyme Inhibitors Histone Deacetylase Inhibitors Histones Hydroxamic Acids Peptides trapoxin A trichostatin A Histone Deacetylases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Van Lint C
Laboratory of Molecular Virology, Picower Institute for Medical Research, Manhasset, NY 11030, USA.
Emiliani S
Verdin E
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Article Info
Journal
Gene expression
Abbr.
Gene Expr
ISSN
1052-2166
Published
1996-00-00
Pages
245-53
Language
English
Region
United States
NLM ID
9200651
PMCID
PMC6138027
Subset
IM
Grants
NIGMS NIH HHS · R01 GM051671 · United States
NIGMS NIH HHS · GM51671-01A1 · United States
External Links
PubMed source PMC Full Text View journal details
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