The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis

Manabu Shirai, Tomoaki Osugi, Hideyuki Koga, Yoshikazu Kaji, Eiki Takimoto, Issei Komuro, Junichi Hara, Takeshi Miwa, Keiko Yamauchi-Takihara, Yoshihiro Takihara

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)177-184
Number of pages8
JournalJournal of Clinical Investigation
Volume110
Issue number2
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Medicine(all)

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    Shirai, M., Osugi, T., Koga, H., Kaji, Y., Takimoto, E., Komuro, I., Hara, J., Miwa, T., Yamauchi-Takihara, K., & Takihara, Y. (2002). The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis. Journal of Clinical Investigation, 110(2), 177-184. https://doi.org/10.1172/JCI200214839