Coordinated expression of p300 and HDAC3 upregulates histone acetylation during dentinogenesis.

Coordinated expression of p300 and HDAC3 upregulates histone acetylation during dentinogenesis.
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p300 和 HDAC3 的协调表达上调牙本质发生过程中的组蛋白乙酰化

DOI:
10.1002/jcb.29470
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发表时间:
2020-03
影响因子:
4
通讯作者:
Liu H
Liu H
中科院分区:
生物学2区
文献类型:
--
作者:
Tao H;Li Q;Lin Y;Zuo H;Cui Y;Chen S;Chen Z;Liu H

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细胞分化是由基因表达受到高度调控的修饰所引起的,但很少涉及DNA序列本身的改变。组蛋白乙酰化是一种主要的表观遗传因素,它将一个乙酰基添加到组蛋白上,从而改变它们与DNA和核蛋白的相互作用。阐明牙本质形成过程中的组蛋白乙酰化对于成牙本质细胞分化和牙本质形成是重要的。在当前的研究中,我们旨在发现组蛋白3赖氨酸9(H3K9ac)和H3K27ac的乙酰化在牙本质形成过程中的作用和调控。我们首先发现这两种修饰在成牙本质细胞分化和牙本质形成过程中都增强。这些修饰由组蛋白乙酰转移酶(HATs)和去乙酰化酶(HDACs)动态催化,其中在成牙本质细胞分化过程中HDAC3降低而p300增加。此外,HDAC3的过表达或p300的敲低在体外抑制成牙本质细胞分化,并且用曲古抑菌素A或C646抑制HDAC3和p300可调节成牙本质细胞分化。综上所述,我们目前的研究结果表明,组蛋白乙酰化参与牙本质形成,并通过上调组蛋白乙酰化来协调p300和HDAC3调控的成牙本质细胞分化的表达。
Cellular differentiation is caused by highly controlled modifications in the gene expression but rarely involves a change in the DNA sequence itself. Histone acetylation is a major epigenetic factor that adds an acetyl group to histone proteins, thus altering their interaction with DNA and nuclear proteins. Illumination of the histone acetylation during dentinogenesis is important for odontoblast differentiation and dentinogenesis. In the current study, we aimed to discover the roles and regulation of acetylation at histone 3 lysine 9 (H3K9ac) and H3K27ac during dentinogenesis. We first found that both of these modifications were enhanced during odontoblast differentiation and dentinogenesis. These modifications are dynamically catalyzed by histone acetyltransferases (HATs) and deacetylases (HDACs), among which HDAC3 was decreased while p300 increased during odontoblast differentiation. Moreover, overexpression of HDAC3 or knockdown p300 inhibited odontoblast differentiation in vitro, and inhibition of HDAC3 and p300 with trichostatin A or C646 regulated odontoblast differentiation. Taken together, the results of our present study suggest that histone acetylation is involved in dentinogenesis and coordinated expression of p300‐ and HDAC3‐regulated odontoblast differentiation through upregulating histone acetylation.
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