Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias.
Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias.
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DOI：
10.1038/srep11204
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发表时间：
2015-06-15
影响因子：
4.6
通讯作者：
Matsuishi T
中科院分区：
文献类型：
--
作者：
Hara M;Takahashi T;Mitsumasu C;Igata S;Takano M;Minami T;Yasukawa H;Okayama S;Nakamura K;Okabe Y;Tanaka E;Takemura G;Kosai K;Yamashita Y;Matsuishi T
甲基化CpG结合蛋白2（MeCP 2）是一种基因表达的表观遗传调节因子，对正常大脑发育至关重要。MeCP 2的突变导致神经元功能受损，并可能导致Rett综合征（RTT），一种神经发育障碍。先前的研究报告了RTT患者和RTT动物模型中的心功能不全，包括心律失常。此外，最近的研究表明MeCP 2可能参与心脏发育和功能障碍，但其在发育和成人心脏中的作用仍然未知。在这项研究中，我们发现Mecp 2缺失的ESCs可以分化为心肌细胞，但心血管祖细胞的发育和进一步分化在MeCP 2缺乏时受到显著影响。此外，我们发现，损失的MeCP 2导致内源性心脏基因和心肌结构的改变失调，虽然Mecp 2-null小鼠没有表现出明显的心脏功能异常。此外，我们检测到Tbx 5基因座中CpG岛的甲基化，并表明MeCP 2可以靶向这些序列。总之，这些结果表明MeCP 2是负责维持正常心脏发育和心肌细胞结构的基因表达程序的重要调节剂。
Methyl-CpG-binding protein 2 (MeCP2) is an epigenetic regulator of gene expression that is essential for normal brain development. Mutations in MeCP2 lead to disrupted neuronal function and can cause Rett syndrome (RTT), a neurodevelopmental disorder. Previous studies reported cardiac dysfunction, including arrhythmias in both RTT patients and animal models of RTT. In addition, recent studies indicate that MeCP2 may be involved in cardiac development and dysfunction, but its role in the developing and adult heart remains unknown. In this study, we found that Mecp2-null ESCs could differentiate into cardiomyocytes, but the development and further differentiation of cardiovascular progenitors were significantly affected in MeCP2 deficiency. In addition, we revealed that loss of MeCP2 led to dysregulation of endogenous cardiac genes and myocardial structural alterations, although Mecp2-null mice did not exhibit obvious cardiac functional abnormalities. Furthermore, we detected methylation of the CpG islands in the Tbx5 locus, and showed that MeCP2 could target these sequences. Taken together, these results suggest that MeCP2 is an important regulator of the gene-expression program responsible for maintaining normal cardiac development and cardiomyocyte structure.
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影响因子：
2.7
作者：
Bissonnette, John M.;Knopp, Sharon J.;Thong, Tran
通讯作者：
Thong, Tran
影响因子：
3.7
作者：
Feng Y;Huang W;Wani M;Yu X;Ashraf M
通讯作者：
Ashraf M
DOI：
10.1083/jcb.201007063
发表时间：
2011-03-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bondue A;Tännler S;Chiapparo G;Chabab S;Ramialison M;Paulissen C;Beck B;Harvey R;Blanpain C
通讯作者：
Blanpain C
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：
--
影响因子：
20.1
作者：
Gutstein, DE;Morley, GE;Fishman, GI
通讯作者：
Fishman, GI