GATA4 mediates gene repression in the mature mouse small intestine through interactions with friend of GATA (FOG) cofactors.
GATA4 mediates gene repression in the mature mouse small intestine through interactions with friend of GATA (FOG) cofactors.
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DOI：
10.1016/j.ydbio.2008.07.022
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发表时间：
2008-10-01
影响因子：
2.7
通讯作者：
Krasinski, Stephen D.
中科院分区：
文献类型：
--
作者：
Beuling, Eva;Bosse, Tjalling;aan de Kerk, Daniel J.;Piaseckyj, Christina M.;Fujiwara, Yuko;Katz, Samuel G.;Orkin, Stuart H.;Grand, Richard J.;Krasinski, Stephen D.
关键词：
GATA4是一种转录因子，在近端小肠中表达，但在远端回肠中不表达，通过基因抑制、基因激活和细胞命运决定等多个过程维持近端-远端的分化。GATA之友(Friend of GATA，FOG)是一个进化保守的辅因子家族，其成员与GATA因子密切相关，在多种组织中介导GATA调节的抑制作用。使用一种新的，可诱导的，肠道特异的GATA4敲入小鼠模型，其中野生型GATA4在小肠被特异性灭活，但一个不结合雾辅助因子的GATA4突变体(GATA4ki)继续表达，我们发现回肠特异基因在小肠近端显著诱导(P<；0.01)；相反，限制近端小肠和细胞谱系标记的基因没有受到影响，表明GATA4-FOG相互作用特定地促进了GATA4在这个器官内的抑制功能。在肠上皮细胞中，FOG1蛋白与GATA4共表达，提示FOG1可能是GATA4在小肠中的调节因子。我们的数据首次表明FOG在哺乳动物小肠中的功能和表达。
GATA4, a transcription factor expressed in the proximal small intestine but not in the distal ileum, maintains proximal-distal distinctions by multiple processes involving gene repression, gene activation, and cell fate determination. Friend of GATA (FOG) is an evolutionarily conserved family of cofactors whose members physically associate with GATA factors and mediate GATA-regulated repression in multiple tissues. Using a novel, inducible, intestine-specific Gata4 knock-in model in mice, in which wild-type GATA4 is specifically inactivated in the small intestine, but a GATA4 mutant that does not bind FOG cofactors (GATA4ki) continues to be expressed, we found that ileal-specific genes were significantly induced in the proximal small intestine (P<0.01); in contrast, genes restricted to proximal small intestine and cell lineage markers were unaffected, indicating that GATA4-FOG interactions contribute specifically to the repression function of GATA4 within this organ. Fog1 mRNA displayed a proximal-distal pattern that parallels that of Gata4, and FOG1 protein was co-expressed with GATA4 in intestinal epithelial cells, implicating FOG1 as the likely mediator of GATA4 function in the small intestine. Our data are the first to indicate FOG function and expression in the mammalian small intestine.
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影响因子：
16
作者：
Crispino, JD;Lodish, MB;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
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