Down-regulation of histone deacetylases stimulates adipocyte differentiation
Down-regulation of histone deacetylases stimulates adipocyte differentiation
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DOI：
10.1074/jbc.m508982200
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发表时间：
2006-03-10
影响因子：
4.8
通讯作者：
Kim, JB
中科院分区：
文献类型：
--
作者：
Yoo, EJ;Chung, JJ;Kim, JB
特定细胞类型的分化是由基因表达的程序性调节驱动的，这是转录机制和染色质重塑因子协调调节的结果。我们提出的证据表明，组蛋白脱乙酰酶的下调是脂肪细胞分化过程中的一个重要过程。在3T3-L1细胞中，在脂肪细胞分化过程中，成脂基因的启动子区域选择性地诱导组蛋白高乙酰化。有趣的是，伴随着包括HDAC1、-2和-5在内的几种组蛋白脱乙酰酶表达水平的急剧下降以及整体组蛋白脱乙酰酶活性的降低。丁酸钠抑制组蛋白脱乙酰酶活性可刺激成脂基因表达和脂肪细胞分化。在3T3-L1细胞中，HDAC1基因下调可促进脂肪细胞的分化，而HDAC1过表达则抑制脂肪细胞的分化。综上所述，这些结果表明，不仅对成脂转录因子的调控，而且对染色质修饰酶的调控对真正的成脂至关重要。
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.