Telephone: 212-659-9691; Fax: 212-849-2442
Embryonic Stem Cells/Induced Pluripotent Stem Cells
Version of Record online: 26 AUG 2009
Copyright © 2009 AlphaMed Press
Volume 27, Issue 12, pages 2884–2895, December 2009
How to Cite
Zhang, H., Fraser, S. T., Papazoglu, C., Hoatlin, M. E. and Baron, M. H. (2009), Transcriptional Activation by the Mixl1 Homeodomain Protein in Differentiating Mouse Embryonic Stem Cells. STEM CELLS, 27: 2884–2895. doi: 10.1002/stem.203
Author contributions: H.Z., S.T.F., M.E.H., and M.H.B.: conception and design; H.Z., S.T.F., and C.P.: collection and assembly of data; H.Z., S.T.F., C.P., and M.H.B.: data analysis and interpretation; M.E.H.: provision of study material; H.Z., S.T.F., and M.H.B.: manuscript writing; H.Z. and M.H.B.: financial support; M.H.B.: final approval of manuscript.
First published online in STEM CELLS EXPRESS August 26, 2009.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue online: 14 DEC 2009
- Version of Record online: 26 AUG 2009
- Accepted manuscript online: 26 AUG 2009 12:00AM EST
- Manuscript Accepted: 6 AUG 2009
- Manuscript Received: 16 MAR 2009
- NIH. Grant Numbers: KO1 DK070752, RO1 HL62248, EB02209
- Transcription factor;
- Mouse embryonic stem cells;
- Mesoderm induction;
Members of the Mix/Bix family of paired class homeobox genes play important roles in the development of vertebrate mesoderm and endoderm. The single Mix/Bix family member identified in the mouse, Mix-like 1 (Mixl1), is required for mesendoderm patterning during gastrulation and promotes mesoderm formation and hematopoiesis in embryonic stem cell (ESC)-derived embryoid bodies. Despite its crucial functions the transcriptional activity and targets of Mixl1 have not been well described. To investigate the molecular mechanisms of Mixl1-mediated transcriptional regulation, we have characterized the DNA-binding specificity and transcriptional properties of this homeodomain protein in differentiating ESCs. Mixl1 binds preferentially as a dimer to an 11-base pair (bp) Mixl1 binding sequence (MBS) that contains two inverted repeats separated by a 3-bp spacer. The MBS mediates transcriptional activation by Mixl1 in both NIH 3T3 cells and in a new application of an inducible ESC differentiation system. Consistent with our previous observation that early induction of Mixl1 expression in ESCs results in premature activation of Goosecoid (Gsc), we have found that Mixl1 occupies two variant MBSs within and activates transcription from the Gsc promoter in vitro and in vivo. These results strongly suggest that Gsc is a direct target gene of Mixl1 during embryogenesis. STEM CELLS 2009;27:2884–2895