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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2017 ; 292
(45
): 18592-18607
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Casein kinase 2-mediated phosphorylation of Brahma-related gene 1 controls
myoblast proliferation and contributes to SWI/SNF complex composition
#MMPMID28939766
Padilla-Benavides T
; Nasipak BT
; Paskavitz AL
; Haokip DT
; Schnabl JM
; Nickerson JA
; Imbalzano AN
J Biol Chem
2017[Nov]; 292
(45
): 18592-18607
PMID28939766
show ga
Transcriptional regulation is modulated in part by chromatin-remodeling enzymes
that control gene accessibility by altering chromatin compaction or nucleosome
positioning. Brahma-related gene 1 (Brg1), a catalytic subunit of the mammalian
SWI/SNF chromatin-remodeling enzymes, is required for both myoblast proliferation
and differentiation, and the control of Brg1 phosphorylation by calcineurin,
PKC?1, and p38 regulates the transition to differentiation. However, we
hypothesized that Brg1 activity might be regulated by additional kinases. Here,
we report that Brg1 is also a target of casein kinase 2 (CK2), a serine/threonine
kinase, in proliferating myoblasts. We found that CK2 interacts with Brg1, and
mutation of putative phosphorylation sites to non-phosphorylatable (Ser to Ala,
SA) or phosphomimetic residues (Ser to Glu, SE) reduced Brg1 phosphorylation by
CK2. Although BRG1-deleted myoblasts that ectopically express the SA-Brg1 mutant
proliferated similarly to the parental cells or cells ectopically expressing
wild-type (WT) Brg1, ectopic expression of the SE-Brg1 mutant reduced
proliferation and increased cell death, similar to observations from cells
lacking Brg1. Moreover, pharmacological inhibition of CK2 increased myoblast
proliferation. Furthermore, the Pax7 promoter, which controls expression of a key
transcription factor required for myoblast proliferation, was in an inaccessible
chromatin state in the SE-Brg1 mutant, suggesting that hyperphosphorylated Brg1
cannot remodel chromatin. WT-, SA-, and SE-Brg1 exhibited distinct differences in
interacting with and affecting expression of the SWI/SNF subunits Baf155 and
Baf170 and displayed differential sub-nuclear localization. Our results indicate
that CK2-mediated phosphorylation of Brg1 regulates myoblast proliferation and
provides insight into one mechanism by which composition of the mammalian SWI/SNF
enzyme complex is regulated.