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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Griffin, Courtney T. Muthukumar, Vijay Curtis, Carol D. Davis, Reema B. Magnuson, Terry |
| Description | Author Affiliation: Griffin CT ( Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. courtney-griffin@omrf.org); |
| Abstract | The ATP-dependent chromatin-remodeling enzyme brahma-related gene 1 (BRG1) regulates transcription of specific target genes during embryonic and postnatal development. Deletion of Brg1 from embryonic blood vessels results in yolk sac vascular remodeling defects. We now report that misregulation of the canonical Wnt signaling pathway underlies many Brg1 mutant vascular phenotypes. Brg1 deletion resulted in down-regulation of several Wnt receptors of the frizzled family, degradation of the intracellular Wnt signaling molecule ß-catenin, and an overall decrease in Wnt signaling in endothelial cells. Pharmacological stabilization of ß-catenin significantly rescued Brg1 mutant vessel morphology and transcription of Wnt target genes. Our data demonstrate that BRG1 impacts the canonical Wnt pathway at two different levels in vascular endothelium: through transcriptional regulation of both Wnt receptor genes and Wnt target genes. These findings establish an epigenetic mechanism for the modulation of Wnt signaling during embryonic vascular development. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA Helicases Metabolism Embryo, Mammalian Embryonic Development Physiology Gene Expression Regulation, Developmental Neovascularization, Physiologic Nuclear Proteins Signal Transduction Transcription Factors Wnt Proteins Animals Cell Line Genetics Down-Regulation Cytology Endothelial Cells Endothelium, Vascular Embryology Epigenesis, Genetic Frizzled Receptors Gene Deletion Mice Mice, Transgenic Transcription, Genetic Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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