Gene expression and IG-DMR hypomethylation of maternally expressed gene 3 in developing corticospinal neurons
Gene expression and IG-DMR hypomethylation of maternally expressed gene 3 in developing corticospinal neurons
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发育中皮质脊髓神经元母源表达基因 3 的基因表达和 IG-DMR 低甲基化
DOI：
10.1016/j.gep.2012.11.003
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发表时间：
2013-01-01
影响因子：
1.2
通讯作者：
Chen, Jie-Guang
中科院分区：
文献类型：
--
作者：
Qu, Chunsheng;Jiang, Tian;Chen, Jie-Guang
哺乳动物的大脑皮层在高级认知功能和复杂的运动控制任务中起着核心作用。母系表达基因3（Meg 3）在大脑皮层发育和神经退行性变中起重要作用，但Meg 3在大脑皮层的表达和调控尚不清楚。在这项研究中，我们研究了Meg 3的转录变体在发育中的小鼠大脑皮层中的表达。通过原位杂交，我们发现，一种新的转录变体的Meg 3与8个小的外显子在发育中的皮质中表达，而长的异构体的Meg 3（类似于11 kb）丰富的皮质脊髓神经元（CSNs）在第V层的皮质。在E12.5的神经祖细胞中未发现Meg 3的转录变异，此时Meg 3附近的基因间差异甲基化区域（IG-DMR）高度甲基化。IG-DMR在E15.5时脱甲基化，并在从Fezf 2-EGFP转基因小鼠分离的早期CSN中保持低甲基化。Meg 3转录变体1的表达与发育过程中IG-DMR甲基化水平呈负相关。此外，父系表达的基因Peg 11的表达仅限于上层，这与母系表达的基因可能优先在皮层的下层转录的想法一致。Meg 3的时空表达模式表明，它可能参与了CSNs的早期发展，并有助于Meg 3异常印迹相关的皮质功能障碍。(C)2012 Elsevier B. V.保留所有权利。
The mammalian cerebral cortex plays a central role in higher cognitive functions and in the complex task of motor control. Maternally expressed gene 3 (Meg3) appears to play a role in cortical development and neurodegeneration, but the expression and regulation of Meg3 in the cortex is not clear. In this study, we examined the expression of transcript variants of Meg3 in the developing mouse cerebral cortex. By in situ hybridization, we found that a novel transcript variant of Meg3 with 8 small exons was expressed in the developing cortex, whereas the long isoforms of Meg3 (similar to 11 kb) were enriched in corticospinal neurons (CSNs) in layer V of the cortex. No transcript varianfs of Meg3 were found in the neural progenitors at E12.5, when the intergenic differential methylation region (IG-DMR) near Meg3 was highly methylated. IG-DMR became demethylated at E15.5 and remained hypomethylated in early CSNs isolated from Fezf2-EGFP transgenic mice. The expression of Meg3 transcript variant 1 was inversely correlated with the IG-DMR methylation level during development. Moreover, expression of paternally expressed gene Peg11 was limited to the upper layers, consistent with the idea that the maternally expressed gene may be preferentially transcribed in the lower layers of the cortex. The spatiotemporal expression pattern of Meg3 suggests that it may participate in the early development of CSNs and contribute to cortical malfunctions related to aberrant imprinting in Meg3. (C) 2012 Elsevier B.V. All rights reserved.