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Exendin‐4 induction of Egr‐1 expression in INS‐1 β‐cells: Interaction of SRF, not YY1, with SRE site of rat Egr‐1 promoter
Author(s) -
Kim MyungJun,
Kang JungHoon,
Chang SeoYoon,
Jang HyunJong,
Ryu Gyeong Ryul,
Ko Seung Hyun,
Jeong InKyung,
Kim MyungSuk,
Jo YangHyeok
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21783
Subject(s) - serum response factor , serum response element , microbiology and biotechnology , transcription factor , yy1 , creb , chemistry , electrophoretic mobility shift assay , biology , promoter , gene expression , gene , biochemistry
Glucagon‐like peptide‐1 (GLP‐1) induces several immediate early response genes such as c‐fos, c‐jun, and early growth response‐1 (Egr‐1), which are involved in cell proliferation and differentiation. We recently reported that exendin‐4 (EX‐4), a potent GLP‐1 agonist, upregulated Egr‐1 expression via phosphorylation of CREB, a transcription factor in INS‐1 β‐cells. This study was designed to investigate the role of another transcription factors, serum response factor (SRF) and Yin Yang‐1 (YY1), in EX‐4‐induced Egr‐1 expression. EX‐4 significantly increased Egr‐1 mRNA and subsequently its protein level. EX‐4‐induced Egr‐1 expression was inhibited by pretreatment with a PKA inhibitor, H‐89, and an MEK inhibitor, PD 98059. The siRNA‐mediated inhibition of PKA and ERK1 resulted in significant reduction of EX‐4‐induced Egr‐1 expression. Promoter analyses showed that SRE clusters were essential for Egr‐1 transcription, and YY1 overexpression did not affect Egr‐1 promoter activity. EMSA results demonstrated that EX‐4‐induced transient increase in DNA–protein complex on SRE site, and that both SRF and phospho‐SRF were bound to this site. Treatment of either YY1 consensus oligonucleotide or YY1 antibody did not effect the change of density or migration of the DNA–protein complex. Collectively, EX‐4‐induced Egr‐1 expression is largely dependent on cAMP‐mediated extracellular signal‐regulated kinase activation, and EX‐4 induces Egr‐1 transcription via the interaction of SRF and phospho‐SRF to SRE sites. J. Cell. Biochem. 104: 2261–2271, 2008. © 2008 Wiley‐Liss, Inc.