The Kruppel-like transcription factor KLF13 is a novel regulator of heart development
The Kruppel-like transcription factor KLF13 is a novel regulator of heart development
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DOI：
10.1038/sj.emboj.7601379
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发表时间：
2006-11-01
期刊：
影响因子：
11.4
通讯作者：
Nemer, Mona
中科院分区：
文献类型：
--
作者：
Lavallee, Genevieve;Andelfinger, Gregor;Nemer, Mona
在人类中，先天性心脏缺陷发生在活产的1-2％，但在大多数情况下，分子机制和致病基因仍然未识别。我们发现了一种对心脏形态发生重要的新型转录途径。我们报告说，KLF13是Kruppel样锌指蛋白家族的成员，主要在心脏中表达，在心脏启动子上结合了进化保守的调节元素，并激活心脏转录。 KLF13在跨物种之间是保守的，而在异爪蟾胚胎中的KLF13敲低会导致心房间隔缺陷，而低颗粒状的低沉淀类似于在人类或具有肌H型GATA-4等位基因的小鼠中观察到的。与剂量敏感的心脏调节剂GATA-4的物理和功能相互作用为心脏中KLF13作用提供了一种机械解释。数据表明，KLF13是心脏发展所需的转录网络的重要组成部分，并表明KLF13是GATA-4修饰符。通过类似于其他GATA-4合作者，KLF13中的突变可能对先天性人心脏病是病因。
In humans, congenital heart defects occur in 1-2% of live birth, but the molecular mechanisms and causative genes remain unidentified in the majority of cases. We have uncovered a novel transcription pathway important for heart morphogenesis. We report that KLF13, a member of the Kruppel-like family of zinc-finger proteins, is expressed predominantly in the heart, binds evolutionarily conserved regulatory elements on cardiac promoters and activates cardiac transcription. KLF13 is conserved across species and knockdown of KLF13 in Xenopus embryos leads to atrial septal defects and hypotrabeculation similar to those observed in humans or mice with hypomorphic GATA-4 alleles. Physical and functional interaction with GATA-4, a dosage-sensitive cardiac regulator, provides a mechanistic explanation for KLF13 action in the heart. The data demonstrate that KLF13 is an important component of the transcription network required for heart development and suggest that KLF13 is a GATA-4 modifier; by analogy to other GATA-4 collaborators, mutations in KLF13 may be causative for congenital human heart disease.