Down-regulation of Histone Deacetylases Stimulates Adipocyte Differentiation

Autor: Sung Sik Choe, Jun-Jae Chung, Eung Jae Yoo, Jae Bum Kim, Kang Ho Kim
Rok vydání: 2006
Předmět:
Zdroj: Journal of Biological Chemistry. 281:6608-6615
ISSN: 0021-9258
DOI: 10.1074/jbc.m508982200
Popis: Specific cell type differentiation is driven by programmed regulation of gene expression, which is the result of coordinated modulation of the transcription machinery and chromatin-remodeling factors. We present evidence here that the down-regulation of histone deacetylases is an important process during adipocyte differentiation. In 3T3-L1 cells, histone hyperacetylation was selectively induced at the promoter regions of adipogenic genes during adipocyte differentiation. Interestingly, this was accompanied by a dramatic decrease in the expression level of several histone deacetylases including HDAC1, -2, and -5 and a reduction in overall histone deacetylase enzyme activity. Inhibition of histone deacetylase activity using sodium butyrate resulted in stimulation of adipogenic gene expression and adipocyte differentiation. Consistently, HDAC1 knock-down promoted adipogenesis whereas HDAC1 overexpression attenuated adipocyte differentiation in 3T3-L1 cells. Together, these results suggest that the regulation of not only adipogenic transcription factors, but also chromatin-modifying enzymes is crucial for the execution of bona fide adipogenesis.
Databáze: OpenAIRE