Redundant Control of Adipogenesis by Histone Deacetylases 1 and 2

Redundant Control of Adipogenesis by Histone Deacetylases 1 and 2
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DOI:
10.1074/jbc.m109.081679
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发表时间:
2010-05-07
影响因子:
4.8
通讯作者:
Olson, Eric N.
Olson, Eric N.
中科院分区:
生物学2区
文献类型:
--
作者:
Haberland, Michael;Carrer, Michele;Olson, Eric N.

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脂肪细胞分化是一个明确的过程,是在转录激活因子和抑制因子的控制下。我们发现,组蛋白去乙酰化酶(HDAC)抑制剂有效地阻止脂肪细胞分化在体外。这种作用对脂肪生成是特异性的,因为另一种间充质分化过程成骨细胞生成在HDAC抑制后增强。通过培养的间充质前体细胞中HDAC基因的系统性遗传缺失,我们表明HDAC 1和HDAC 2的缺失导致脂质积累减少,揭示了这些I类HDAC在脂肪形成中的冗余和必要作用。这些发现揭示了HDAC在控制脂肪形成中的先前未被认识的作用。
Adipocyte differentiation is a well defined process that is under the control of transcriptional activators and repressors. We show that histone deacetylase (HDAC) inhibitors efficiently block adipocyte differentiation in vitro. This effect is specific to adipogenesis, as another mesenchymal differentiation process, osteoblastogenesis, is enhanced upon HDAC inhibition. Through the systematic genetic deletion of HDAC genes in cultured mesenchymal precursor cells, we show that deletion of HDAC1 and HDAC2 leads to reduced lipid accumulation, revealing redundant and requisite roles of these class I HDACs in adipogenesis. These findings unveil a previously unrecognized role for HDACs in the control of adipogenesis.