Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation

Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation

August 29, 2000 | Victoria M. Richon*, Todd W. Sandhoff, Richard A. Rifkind, and Paul A. Marks
The study investigates the effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, on the expression of the cell cycle kinase inhibitor p21WAF1 and histone acetylation in T24 bladder carcinoma cells. SAHA induces the upregulation of p21WAF1 mRNA and protein levels, which is associated with an increase in the transcription rate of the p21WAF1 gene. This induction is accompanied by a transient accumulation of acetylated histones H3 and H4 in the chromatin associated with the p21WAF1 gene promoter and coding regions. The increase in acetylation is selective, as it does not affect the expression of other genes such as actin and p27. The findings suggest that SAHA-induced histone acetylation is targeted to specific genes and plays a role in the selective activation of p21WAF1.The study investigates the effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, on the expression of the cell cycle kinase inhibitor p21WAF1 and histone acetylation in T24 bladder carcinoma cells. SAHA induces the upregulation of p21WAF1 mRNA and protein levels, which is associated with an increase in the transcription rate of the p21WAF1 gene. This induction is accompanied by a transient accumulation of acetylated histones H3 and H4 in the chromatin associated with the p21WAF1 gene promoter and coding regions. The increase in acetylation is selective, as it does not affect the expression of other genes such as actin and p27. The findings suggest that SAHA-induced histone acetylation is targeted to specific genes and plays a role in the selective activation of p21WAF1.
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[slides and audio] Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation.