The Transcription Factor Atonal homolog 8 Regulates Gata4 and Friend of Gata-2 during Vertebrate Development
The Transcription Factor Atonal homolog 8 Regulates Gata4 and Friend of Gata-2 during Vertebrate Development
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DOI：
10.1074/jbc.m113.463083
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发表时间：
2013-08-23
影响因子：
4.8
通讯作者：
Kahn, Mark L.
中科院分区：
文献类型：
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作者：
Rawnsley, David R.;Xiao, Jiping;Kahn, Mark L.
GATA和GATA之友（FOG）形成一个转录复合体，在鱼类和哺乳动物的心血管发育中起关键作用。在本研究中，我们证明了基本的螺旋-环-螺旋转录因子同源物8 （Atoh8）是鱼类心脏发育所必需的，而不是小鼠。遗传学研究表明，在鱼的心脏和鱼鳔发育过程中，Atoh8与Gata4和Fog1特异性相互作用。生化研究表明，ATOH8、GATA4和FOG2在体外一个复合体中结合。与鱼类相反，ATOH8缺陷小鼠表现出正常的心脏发育，ATOH8的缺失不会改变Gata4（+/-）小鼠的心脏发育。这种ATOH8作用的物种差异部分是由LacZ和GFP报告等位基因解释的，它们揭示了ATOH8在小鼠心房心肌而不是心室心肌的表达限制。我们的研究发现，ATOH8是一种新的GATA-FOG功能调节剂，它是鱼类而不是小鼠心脏发育所必需的。在哺乳动物中，ATOH8是否在其他位点或以更微妙的方式调节GATA-FOG功能尚不清楚。
GATA and Friend of GATA (FOG) form a transcriptional complex that plays a key role in cardiovascular development in both fish and mammals. In the present study we demonstrate that the basic helix-loop-helix transcription factor Atonal homolog 8 (Atoh8) is required for development of the heart in fish but not in mice. Genetic studies reveal that Atoh8 interacts specifically with Gata4 and Fog1 during development of the heart and swim bladder in the fish. Biochemical studies reveal that ATOH8, GATA4, and FOG2 associate in a single complex in vitro. In contrast to fish, ATOH8-deficient mice exhibit normal cardiac development and loss of ATOH8 does not alter cardiac development in Gata4(+/-) mice. This species difference in the role of ATOH8 is explained in part by LacZ and GFP reporter alleles that reveal restriction of Atoh8 expression to atrial but not ventricular myocardium in the mouse. Our findings identify ATOH8 as a novel regulator of GATA-FOG function that is required for cardiac development in the fish but not the mouse. Whether ATOH8 modulates GATA-FOG function at other sites or in more subtle ways in mammals is not yet known.