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Cell Rep. 2015 Mar 31;10(12):2032-42. doi: 10.1016/j.celrep.2015.02.054. Epub 2015 Mar 19.

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

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
2
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
3
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
4
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: roland.stein@vanderbilt.edu.

Abstract

Pdx1 is a transcription factor of fundamental importance to pancreas formation and adult islet β 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 β 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 β cell activity.

PMID:
25801033
PMCID:
PMC4651178
DOI:
10.1016/j.celrep.2015.02.054
[Indexed for MEDLINE]
Free PMC Article

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