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1: Biochem Biophys Res Commun. 2005 Aug 12;333(4):1361-9.Click here to read Links

Transcriptional regulation of the homeobox gene Mixl1 by TGF-beta and FoxH1.

Hart AH, Willson TA, Wong M, Parker K, Robb L.

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade Parkville 3050, Vic., Australia. hart@wehi.edu.au

Mixl1 is a paired-type homeodomain protein that plays a crucial role in morphogenesis and endoderm differentiation in the murine embryo. To understand how Mixl1 directs embryogenesis, we studied the regulation of Mixl1 expression at a transcriptional level. In HepG2 cells, a genomic fragment encompassing the Mixl1 promoter conferred strong TGF-beta-induced transcription that was dependent on the presence of the DNA-binding protein FoxH1. Further analysis of the Mixl1 promoter identified a proximal response element (PRE) containing SMAD- and FoxH1-binding sites required for TGF-beta responsiveness. The PRE was also responsive to signalling by Nodal, a TGF-beta ligand required for normal embryonic patterning. These results demonstrate for the first time a functional role for TGF-beta ligands in regulation of mammalian Mixl1, identify FoxH1 as an essential transcriptional co-activator, and implicate Nodal as the embryonic regulator of Mixl1 in mesendoderm morphogenesis.

PMID: 15982639 [PubMed - indexed for MEDLINE]