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Publication : Dynamic recruitment of functionally distinct Swi/Snf chromatin remodeling complexes modulates Pdx1 activity in islet β cells.

First Author  McKenna B Year  2015
Journal  Cell Rep Volume  10
Issue  12 Pages  2032-42
PubMed ID  25801033 Mgi Jnum  J:316508
Mgi Id  MGI:6837687 Doi  10.1016/j.celrep.2015.02.054
Citation  McKenna B, et al. (2015) Dynamic recruitment of functionally distinct Swi/Snf chromatin remodeling complexes modulates Pdx1 activity in islet beta cells. Cell Rep 10(12):2032-42
abstractText  Pdx1 is a transcription factor of fundamental importance to pancreas formation and adult islet beta 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 beta 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 beta cell activity.
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