H3K9ac and HDAC2 Activity Are Involved in the Expression of Monocarboxylate Transporter 1 in Oligodendrocyte.
H3K9ac and HDAC2 Activity Are Involved in the Expression of Monocarboxylate Transporter 1 in Oligodendrocyte.
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DOI：
10.3389/fnmol.2017.00376
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发表时间：
2017
影响因子：
4.8
通讯作者：
Fan H
中科院分区：
文献类型：
--
作者：
Lai Q;Du W;Wu J;Wang X;Li X;Qu X;Wu X;Dong F;Yao R;Fan H
最近，有报道称单羧酸转运蛋白1（MCT1）在少突胶质细胞分化和髓鞘形成中发挥着至关重要的作用。我们发现MCT1在少突胶质细胞中强表达，但在少突胶质细胞前体细胞（OPC）中弱表达，并且其潜在机制仍然难以捉摸。组蛋白脱乙酰酶 (HDAC) 活性是诱导少突胶质细胞分化和成熟所必需的。我们询问 HDAC 是否参与 MCT1 表达的调节。这项工作揭示了 OPC 中 mct1 基因 (Slc16a1) 启动子中组蛋白 H3K9 (H3K9ac) 的乙酰化水平远高于少突胶质细胞中的乙酰化水平。 HDAC 乙酰转移酶抑制剂曲古抑菌素 A 和姜黄素证实 H3K9ac 调节 MCT1 表达。值得注意的是，少突胶质细胞中 H3K9ac 和 MCT1 表达呈负相关。此外，我们发现少突胶质细胞中HDAC1、2和3蛋白的水平明显高于OPCs。然而，特异性敲低 HDAC2（而非 HDAC1 和 HDAC3）会显着降低少突胶质细胞中 MCT1 的表达。相反，HDAC2 的过表达显着增强了 MCT1 的表达。结果表明，HDAC2 参与了 H3K9ac 修饰，从而在少突胶质细胞发育过程中调节 MCT1 的表达。
Recently, it is reported that monocarboxylate transporter 1 (MCT1) plays crucial role in oligodendrocyte differentiation and myelination. We found that MCT1 is strongly expressed in oligodendrocyte but weakly expressed in oligodendrocyte precursors (OPCs), and the underlying mechanisms remain elusive. Histone deacetylases (HDACs) activity is required for induction of oligodendrocyte differentiation and maturation. We asked whether HDACs are involved in the regulation of MCT1 expression. This work revealed that the acetylation level of histone H3K9 (H3K9ac) was much higher in mct1 gene (Slc16a1) promoter in OPCs than that in oligodendrocyte. H3K9ac regulates MCT1 expression was confirmed by HDAC acetyltransferase inhibitors trichostatin A and curcumin. Of note, there was a negative correlation between H3K9ac and MCT1 expression in oligodendrocyte. Further, we found that the levels of HDAC1, 2, and 3 protein in oligodendrocyte were obviously higher than those in OPCs. However, specific knockdown of HDAC2 but not HDAC1 and HDAC3 significantly decreased the expression of MCT1 in oligodendrocyte. Conversely, overexpression of HDAC2 remarkably enhanced the expression of MCT1. The results imply that HDAC2 is involved in H3K9ac modification which regulates the expression of MCT1 during the development of oligodendrocyte.
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影响因子：
11.1
作者：
Klosinski LP;Yao J;Yin F;Fonteh AN;Harrington MG;Christensen TA;Trushina E;Brinton RD
通讯作者：
Brinton RD
影响因子：
--
作者：
He, Ye;Sandoval, Juan;Casaccia-Bonnefil, Patrizia
通讯作者：
Casaccia-Bonnefil, Patrizia
影响因子：
5.6
作者：
Gregoretti, IV;Lee, YM;Goodson, HV
通讯作者：
Goodson, HV
影响因子：
4.8
作者：
Balasubramanyam, K;Varier, RA;Kundu, TK
通讯作者：
Kundu, TK
DOI：
10.1038/nrg2485
发表时间：
2009-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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