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MCB Accepts, published online ahead of print on 29 October 2007
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Mol. Cell. Biol. doi:10.1128/MCB.00771-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The PIAS-like Protein Zimp10 is Essential for Embryonic Viability and Proper Vascular Development

Jason Beliakoff, Jane Lee, Hiroo Ueno, Aparna Aiyer, Irving L. Weissman, Gregory S. Barsh, Robert D. Cardiff, and Zijie Sun*

Departments of Urology, Pathology, and Genetics, Stanford University School of Medicine, Stanford, CA 94305-5328; Moores UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093-0819; Department of Comparative Medicine, University of California, Davis, Davis, CA 95616

* To whom correspondence should be addressed. Email: zsun{at}stanford.edu.


   Abstract

Members of the PIAS (Protein Inhibitor of Activated STAT) family play critical roles in modulating the activity of a variety of transcriptional regulators. Zimp10, a novel PIAS-like protein, is a transcriptional co-regulator and may be involved in modification of chromatin through interactions with the SWI/SNF chromatin remodeling complexes. Here, we investigate the biological role of Zimp10 in zimp10-deficient mice. Homozygosity for the Zimp10-targeted allele resulted in developmental arrest at approximately E10.5. Analysis of knockout embryos revealed severe defects in reorganization of the yolk sac vascular plexus. No significant abnormality in hematopoietic potential was observed in zimp10 null mice. Microarray and quantified RT-PCR analyses showed that the expression of the Fos family member Fra1, which is involved in extraembryonic vascular development, was reduced in yolk sac tissues of zimp10-null embryos. Using fra1 promoter/reporter constructs, we further demonstrate the regulatory role of Zimp10 on transcription of Fra-1. This study provides evidence to demonstrate a crucial role for Zimp10 in vasculogenesis.







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