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Publication : Pdgfrα and Flk1 are direct target genes of Mixl1 in differentiating embryonic stem cells.

First Author  Pereira LA Year  2012
Journal  Stem Cell Res Volume  8
Issue  2 Pages  165-79
PubMed ID  22265737 Mgi Jnum  J:190263
Mgi Id  MGI:5448504 Doi  10.1016/j.scr.2011.09.007
Citation  Pereira LA, et al. (2012) Pdgfralpha and Flk1 are direct target genes of Mixl1 in differentiating embryonic stem cells. Stem Cell Res 8(2):165-79
abstractText  The Mixl1 homeodomain protein plays a key role in mesendoderm patterning during embryogenesis, but its target genes remain to be identified. We compared gene expression in differentiating heterozygous Mixl1(GFP/w) and homozygous null Mixl1(GFP/Hygro) mouse embryonic stem cells to identify potential downstream transcriptional targets of Mixl1. Candidate Mixl1 regulated genes whose expression was reduced in GFP+ cells isolated from differentiating Mixl1(GFP/Hygro) embryoid bodies included Pdgfralpha and Flk1. Mixl1 bound to ATTA sequences located in the Pdgfralpha and Flk1 promoters and chromatin immunoprecipitation assays confirmed Mixl1 occupancy of these promoters in vivo. Furthermore, Mixl1 transactivated the Pdgfralpha and Flk1 promoters through ATTA sequences in a DNA binding dependent manner. These data support the hypothesis that Mixl1 directly regulates Pdgfralpha and Flk1 gene expression and strengthens the position of Mixl1 as a key regulator of mesendoderm development during mammalian gastrulation.
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