Down-regulation of histone deacetylases stimulates adipocyte differentiation.
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.
Yoo
Eung Jae
EJ
Department of Biological Sciences and Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, South Korea.
Chung
Jun-Jae
JJ
Choe
Sung Sik
SS
Kim
Kang Ho
KH
Kim
Jae Bum
JB
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000201:enzymology*; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056284:Histone Deacetylase 1; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006657:Histones / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D011401:Promoter Regions, Genetic
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D047495:PPAR gamma; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases