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Dynamic recruitment of functionally distinct Swi/Snf chromatin remodeling
complexes modulates Pdx1 activity in islet ? cells
#MMPMID25801033
McKenna B
; Guo M
; Reynolds A
; Hara M
; Stein R
Cell Rep
2015[Mar]; 10
(12
): 2032-42
PMID25801033
show ga
Pdx1 is a transcription factor of fundamental importance to pancreas formation
and adult islet ? 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 ? 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 ? cell activity.
|Animals
[MESH]
|Cell Differentiation/*genetics
[MESH]
|Cell Line, Tumor
[MESH]
|Cell Nucleus/metabolism
[MESH]
|Chromatin Assembly and Disassembly/*genetics
[MESH]
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