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Serum response factor expression is enriched in pancreatic β cells and regulates insulin gene expression
Author(s) -
Sarkar Aloke,
Zhang Mao,
Liu ShiHe,
Sarkar Swapna,
Brunicardi F. Charles,
Berger David H.,
Belaguli Narasimhaswamy S.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-173757
Subject(s) - gene expression , expression (computer science) , gene , microbiology and biotechnology , medicine , biology , endocrinology , genetics , computer science , programming language
Serum response factor (SRF) is an essential regulator of myogenic and neurogenic genes and the ubiquitously expressed immediate‐early genes. The purpose of this study is to determine SRF expression pattern in murine pancreas and examine the role of SRF in pancreatic gene expression. Immunohistochemical analysis of wild‐type pancreas and LacZ staining of pancreas from SRF LacZ knock‐in animals showed that SRF expression is restricted to β cells. SRF bound to the rat insulin promoter II (RIP II) serum response element, an element conserved in both rat I and murine I and II insulin promoters. SRF activated RIP II, and SRF binding to RIP II and the exon 5‐encoded 64‐aa subdomain of SRF was required for this activation. Transient or stable knockdown of SRF leads to down‐regulation of insulin gene expression, suggesting that SRF is required for insulin gene expression. Further, SRF physically interacted with the pancreas and duodenum homeobox‐1 (Pdx‐1) and synergistically activated RIP II. Elevated glucose concentration down‐regulated SRF binding to RIP II SRE, and this down‐regulation was associated with decreased RIP II activity and increased SRF phosphorylation on serine 103. Together, our results demonstrate that SRF is a glucose concentration‐sensitive regulator of insulin gene expression.—Sarkar, A., Zhang, M., Liu, S.‐H., Sarkar, S., Brunicardi, F. C., Berger, D. H., Belaguli, N. S. Serum response factor expression is enriched in pancreatic β cells and regulates insulin gene expression. FASEB J. 25, 2592–2603 (2011). www.fasebj.org