Transcriptional regulation of the homeobox gene Mixl1 by TGF-beta and FoxH1
- Author(s)
- Hart, AH; Willson, TA; Wong, M; Parker, K; Robb, L;
- Details
- Publication Year 2005-08-12,Volume 333,Issue #4,Page 1361-1369
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Publication Type
- Journal Article
- Abstract
- 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 morpbogenesis. (c) 2005 Elsevier Inc. All rights reserved.
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- GROWTH-FACTOR-BETA; DNA-BINDING; MESODERM DEVELOPMENT; PRIMITIVE STREAK; VENTRAL MESODERM; ACTIVIN; PROMOTER; PROTEIN; MOUSE; SMAD3
- Publisher's Version
- https://doi.org/10.1016/j.bbrc.2005.06.044
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2005-08-12 12:00:00