Cited2, a coactivator of HNF4alpha, is essential for liver development. EMBO J 2007 Oct 31;26(21):4445-56
Date
10/13/2007Pubmed ID
17932483Pubmed Central ID
PMC2063472DOI
10.1038/sj.emboj.7601883Scopus ID
2-s2.0-35648939343 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
The transcriptional modulator Cited2 is induced by various biological stimuli including hypoxia, cytokines, growth factors, lipopolysaccharide (LPS) and flow shear. In this study, we report that Cited2 is required for mouse fetal liver development. Cited2(-/-) fetal liver displays hypoplasia with higher incidence of cell apoptosis, and exhibits disrupted cell-cell contact, disorganized sinusoidal architecture, as well as impaired lipid metabolism and hepatic gluconeogenesis. Furthermore, we demonstrated the physical and functional interaction of Cited2 with liver-enriched transcription factor HNF4alpha. Chromatin immunoprecipitation (ChIP) assays further confirmed the recruitment of Cited2 onto the HNF4alpha-responsive promoters and the reduced HNF4alpha binding to its target gene promoters in the absence of Cited2. Taken together, this study suggests that fetal liver defects in mice lacking Cited2 result, at least in part, from its defective coactivation function for HNF4alpha.
Author List
Qu X, Lam E, Doughman YQ, Chen Y, Chou YT, Lam M, Turakhia M, Dunwoodie SL, Watanabe M, Xu B, Duncan SA, Yang YCMESH terms used to index this publication - Major topics in bold
AnimalsCell Line
Cell Proliferation
DNA-Binding Proteins
Gene Expression Regulation
HeLa Cells
Hepatocyte Nuclear Factor 4
Humans
Liver
Mice
Mice, Transgenic
Phosphorylation
Repressor Proteins
Time Factors
Trans-Activators
