Lai Qingwei, Du Wantong, Wu Jian, Wang Xiao, Li Xinyu, Qu Xuebin, Wu Xiuxiang, Dong Fuxing, Yao Ruiqin, Fan Hongbin
Xuzhou Key Laboratory of Neurobiology, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Front Mol Neurosci. 2017 Nov 14;10:376. doi: 10.3389/fnmol.2017.00376. eCollection 2017.
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 gene () 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.
最近，有报道称单羧酸转运体1（MCT1）在少突胶质细胞分化和髓鞘形成中起关键作用。我们发现MCT1在少突胶质细胞中强烈表达，但在少突胶质细胞前体细胞（OPCs）中弱表达，其潜在机制仍不清楚。组蛋白去乙酰化酶（HDACs）活性是诱导少突胶质细胞分化和成熟所必需的。我们询问HDACs是否参与MCT1表达的调节。这项工作表明，OPCs中基因（）启动子处组蛋白H3K9（H3K9ac）的乙酰化水平远高于少突胶质细胞中的水平。HDAC乙酰转移酶抑制剂曲古抑菌素A和姜黄素证实了H3K9ac调节MCT1表达。值得注意的是，少突胶质细胞中H3K9ac与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中的水平。然而，特异性敲低HDAC2而非HDAC1和HDAC3可显著降低少突胶质细胞中MCT1的表达。相反，HDAC2的过表达显著增强了MCT1的表达。结果表明，HDAC2参与H3K9ac修饰，在少突胶质细胞发育过程中调节MCT1的表达。
