title: Down-regulation of histone deacetylases stimulates adipocyte differentiation.
abstract: 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.
authors.affiliation: Department of Biological Sciences and Research Center for Functional Cellulomics, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Eung Jae
authors.initials: EJ
authors.lastname: Yoo
authors.forename: Jun-Jae
authors.initials: JJ
authors.lastname: Chung
authors.forename: Sung Sik
authors.initials: SS
authors.lastname: Choe
authors.forename: Kang Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D047495:PPAR gamma; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases