CIBZ Regulates Mesodermal and Cardiac Differentiation of by Suppressing T and Mesp1 Expression in Mouse Embryonic Stem Cells.
CIBZ Regulates Mesodermal and Cardiac Differentiation of by Suppressing T and Mesp1 Expression in Mouse Embryonic Stem Cells.
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DOI：
10.1038/srep34188
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发表时间：
2016-09-23
影响因子：
4.6
通讯作者：
Matsuda E
中科院分区：
文献类型：
--
作者：
Kotoku T;Kosaka K;Nishio M;Ishida Y;Kawaichi M;Matsuda E
胚胎干细胞（ESC）中胚层和心脏特化的分子机制尚未完全了解。在这里，我们表明，BTB结构域的锌指蛋白CIBZ表达在小鼠胚胎干细胞，但在ESC分化过程中显着下调。CIBZ在胚胎干细胞中的缺失诱导了向中胚层表型的分化及其向心肌细胞的分化，而CIBZ的过表达延迟了这些过程。在ESC分化期间，CIBZ功能丧失和获得数据表明CIBZ负调节Brachyury（T）和Mesp1的表达，Brachyury（T）和Mesp1是分别负责哺乳动物中胚层和心脏祖细胞特化的关键转录因子。染色质免疫沉淀试验表明，CIBZ结合T和Mesp1启动子在未分化的胚胎干细胞，荧光素酶试验表明，CIBZ抑制T和Mesp1启动子。这些发现表明，CIBZ是一种新的调节剂的中胚层和心脏分化的胚胎干细胞，并表明CIBZ介导的心脏分化依赖于这两个基因的调节。
The molecular mechanisms underlying mesodermal and cardiac specification from embryonic stem cells (ESCs) are not fully understood. Here, we showed that the BTB domain-containing zinc finger protein CIBZ is expressed in mouse ESCs but is dramatically downregulated during ESC differentiation. CIBZ deletion in ESCs induced specification toward mesoderm phenotypes and their differentiation into cardiomyocytes, whereas overexpression of CIBZ delayed these processes. During ESC differentiation, CIBZ loss-and-gain-of-function data indicate that CIBZ negatively regulates the expressions of Brachyury (T) and Mesp1, the key transcriptional factors responsible for the specification of mammalian mesoderm and cardiac progenitors, respectively. Chromatin immunoprecipitation assays showed that CIBZ binds to T and Mesp1 promoters in undifferentiated ESCs, and luciferase assays indicate that CIBZ suppresses T and Mesp1 promoters. These findings demonstrate that CIBZ is a novel regulator of mesodermal and cardiac differentiation of ESCs, and suggest that CIBZ-mediated cardiac differentiation depends on the regulation of these two genes.
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影响因子：
3.7
作者：
Buck-Koehntop BA;Defossez PA
通讯作者：
Defossez PA
影响因子：
3.7
作者：
Evans AL;Faial T;Gilchrist MJ;Down T;Vallier L;Pedersen RA;Wardle FC;Smith JC
通讯作者：
Smith JC
影响因子：
2.6
作者：
Haraguchi, S;Kitajima, S;Saga, Y
通讯作者：
Saga, Y
影响因子：
23.9
作者：
Loh, Kyle M.;Lim, Bing
通讯作者：
Lim, Bing
DOI：
10.1073/pnas.1005847107
发表时间：
2010-07-27
影响因子：
11.1
作者：
Moretto-Zita, Matteo;Jin, Hua;Xu, Yang
通讯作者：
Xu, Yang