Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D.
Dual-specificity tyrosine-phosphorylation regulated kinase 1A Gene Transcription is regulated by Myocyte Enhancer Factor 2D.
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双特异性酪氨酸磷酸化调节激酶 1A 基因转录受肌细胞增强因子 2D 调节
DOI：
10.1038/s41598-017-07655-1
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发表时间：
2017-08-03
影响因子：
4.6
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Wang P;Wang L;Chen L;Sun X
双特异性酪氨酸磷酸化调节激酶1A（DYRK1A）定位于21号染色体的唐氏综合征关键区域。作为与唐氏综合征及阿尔茨海默病（AD）相关学习缺陷的候选致病基因，DYRK1A被认为在细胞增殖和大脑发育中发挥关键作用。肌细胞特异性增强因子2（MEF2）转录因子家族成员MEF2D，已被证实可调控神经元细胞的分化与发育。在此，我们证明MEF2D可通过特异性激活DYRK1A亚型5的基因转录，上调DYRK1A基因的表达。通过荧光素酶报告基因实验、电泳迁移率变动分析（EMSA）及染色质免疫沉淀（ChIP），确定并证实了DYRK1A亚型5启动子区域-268至-254 bp处存在MEF2D反应元件。DYRK1A和MEF2D在小鼠大脑发育过程中的协同表达，表明这两个基因在神经发育过程中可能存在相互作用。MEF2D对DYRK1A的转录调控也会影响DYRK1A的激酶活性。因此，MEF2D对DYRK1A的分子调控进一步支持了二者参与神经发育过程这一观点。
Dual-specificity tyrosine–phosphorylation regulated kinase 1A (DYRK1A) is localized in the Down syndrome critical region of chromosome 21. As a candidate gene responsible for learning defects associated with Down syndrome and Alzheimer’s disease (AD), DYRK1A has been implied to play pivotal roles in cell proliferation and brain development. MEF2D, a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors, was proved to be in control of neuronal cell differentiation and development. Here we demonstrated that MEF2D could upregulate DYRK1A gene expression through specific activation of DYRK1A isoform 5 gene transcription. A MEF2D responsive element from −268 to −254 bp on promoter region of DYRK1A isoform 5 was identified and confirmed by luciferase assay, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). The coordinated expression of DYRK1A and MEF2D in mouse brain development indicated a possibility of the cross-interaction of these two genes during neurodevelopment. The DYRK1A kinase activity was also affected by MEF2D’s transcriptional regulation of DYRK1A. Therefore, the molecular regulation of DYRK1A by MEF2D further supported their involvement in neurodevelopment.
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影响因子：
3.5
作者：
Altafaj, X;Dierssen, M;Estivill, X
通讯作者：
Estivill, X
影响因子：
4.7
作者：
Ryoo, Soo-Ryoon;Cho, Hyun-Jeong;Song, Woo-Joo
通讯作者：
Song, Woo-Joo
影响因子：
3.7
作者：
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Li R
影响因子：
4.2
作者：
Mazur-Kolecka, Bozena;Golabek, Adam;Frackowiak, Janusz
通讯作者：
Frackowiak, Janusz
影响因子：
4.8
作者：
Liu, Fei;Liang, Zhihou;Gong, Cheng-Xin
通讯作者：
Gong, Cheng-Xin