Manipulation of endogenous regulatory elements and transgenic analyses of the Tbx1 gene

Manipulation of endogenous regulatory elements and transgenic analyses of the Tbx1 gene Pharyngeal morphogenesis is a complex process involving precise coordination of multiple cell types and transcription networks. TBX1 heterozygous mutation causes DiGeorge Syndrome, a typical disorder of pharyngeal development. In mice, loss of function of Tbx1 causes severe disruption of pharyngeal development. Therefore, to understand the regulatory circuits controlling the pharyngeal apparatus, it is important to understand how Tbx1 is regulated. Transgenic experiments had shown that a Forkhead (Fox) transcription factor binding site is required for the activity of a Tbx1 enhancer driving expression in many of the endogenous domains. In this study we carried out manipulation of regulatory elements of the endogenous gene in mice and extensive transgenic analysis of the Tbx1 locus. Results indicated that the Fox binding site is dispensable for Tbx1 gene expression, but the enhancer within which it is located regulates, to a limited extent, mesodermal expression of the gene. Transgenic analysis of conserved noncoding regions within 54 kb of the Tbx1 locus identified a novel pharyngeal endoderm-specific enhancer and an intronic suppressor element. Overall, our data suggest a regulatory architecture of the Tbx1 gene made of tissue-specific modules and redundant elements that individually contribute, to a modest extent, to the expression of the gene. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

Manipulation of endogenous regulatory elements and transgenic analyses of the Tbx1 gene

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Publisher
Springer-Verlag
Copyright
Copyright © 2010 by Springer Science+Business Media, LLC
Subject
Life Sciences; Zoology ; Anatomy; Cell Biology
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-010-9304-4
Publisher site
See Article on Publisher Site

Abstract

Pharyngeal morphogenesis is a complex process involving precise coordination of multiple cell types and transcription networks. TBX1 heterozygous mutation causes DiGeorge Syndrome, a typical disorder of pharyngeal development. In mice, loss of function of Tbx1 causes severe disruption of pharyngeal development. Therefore, to understand the regulatory circuits controlling the pharyngeal apparatus, it is important to understand how Tbx1 is regulated. Transgenic experiments had shown that a Forkhead (Fox) transcription factor binding site is required for the activity of a Tbx1 enhancer driving expression in many of the endogenous domains. In this study we carried out manipulation of regulatory elements of the endogenous gene in mice and extensive transgenic analysis of the Tbx1 locus. Results indicated that the Fox binding site is dispensable for Tbx1 gene expression, but the enhancer within which it is located regulates, to a limited extent, mesodermal expression of the gene. Transgenic analysis of conserved noncoding regions within 54 kb of the Tbx1 locus identified a novel pharyngeal endoderm-specific enhancer and an intronic suppressor element. Overall, our data suggest a regulatory architecture of the Tbx1 gene made of tissue-specific modules and redundant elements that individually contribute, to a modest extent, to the expression of the gene.

Journal

Mammalian GenomeSpringer Journals

Published: Nov 25, 2010

References

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