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Publication
Dynamic recruitment of functionally distinct Swi/Snf chromatin remodeling
complexes modulates Pdx1 activity in islet ß cells.
Authors McKenna B, Guo M, Reynolds A, Hara M, Stein R
Submitted By Roland Stein on 7/24/2015
Status Published
Journal Cell reports
Year 2015
Date Published 3/31/2015
Volume : Pages 10 : 2032 - 2042
PubMed Reference 25801033
Abstract Pdx1 is a transcription factor of fundamental importance to pancreas formation
and adult islet ß cell function. However, little is known about the positive-
and negative-acting coregulators recruited to mediate transcriptional control.
Here, we isolated numerous Pdx1-interacting factors possessing a wide range of
cellular functions linked with this protein, including, but not limited to,
coregulators associated with transcriptional activation and repression, DNA
damage response, and DNA replication. Because chromatin remodeling activities
are essential to developmental lineage decisions and adult cell function, our
analysis focused on investigating the influence of the Swi/Snf chromatin
remodeler on Pdx1 action. The two mutually exclusive and indispensable Swi/Snf
core ATPase subunits, Brg1 and Brm, distinctly affected target gene
expression in ß cells. Furthermore, physiological and pathophysiological
conditions dynamically regulated Pdx1 binding to these Swi/Snf complexes
in vivo. We discuss how context-dependent recruitment of coregulatory complexes
by Pdx1 could impact pancreas cell development and adult islet ß cell activity.




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