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J Clin Invest 2002 Jul 01;1102:177-84. doi: 10.1172/JCI14839.
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The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis.

Shirai M , Osugi T , Koga H , Kaji Y , Takimoto E , Komuro I , Hara J , Miwa T , Yamauchi-Takihara K , Takihara Y .

The Polycomb-group (PcG) gene Rae28 is a mammalian homologue of the Drosophila gene polyhomeotic. PcG genes are known to maintain transcription states, once initiated, probably by regulating chromatin structure. Since homozygous Rae28-deficient (Rae28(-/-)) mice displayed cardiac anomalies similar to congenital heart diseases in humans, we examined the role of Rae28 in cardiac morphogenesis at the molecular level. In Rae28(-/-) embryos, expression of the cardiac selector gene Nkx2.5/Csx (Nkx2.5) was initiated properly but was not sufficiently sustained later in development. This impaired expression of Nkx2.5 in the maintenance phase proved to have a crucial effect on cardiac morphogenesis, as demonstrated by the results of a genetic complementation experiment in which the cardiac anomalies were suppressed by overexpression of human NKX2.5/CSX1 in Rae28(-/-) embryos. Ubiquitous expression of exogenous Rae28 likewise restored the impaired Nkx2.5 expression in Rae28(-/-) embryos, further supporting the notion that Rae28 sustains Nkx2.5 expression in cardiomyocytes. Thus, our data show that a mammalian PcG gene can play a key role in organogenesis by helping to maintain the expression of a selector gene.

PubMed ID: 12122109
PMC ID: PMC151044
Article link: J Clin Invest

Species referenced: Xenopus
Genes referenced: nkx2-5 phc1

References [+] :
Akasaka, A role for mel-18, a Polycomb group-related vertebrate gene, during theanteroposterior specification of the axial skeleton. 1996, Pubmed