title: Regulator of G protein signaling 4 is a novel target of GATA-6 transcription factor.
abstract: GATA transcription factors regulate an array of genes important in cell proliferation and differentiation. Here we report the identification of regulator of G protein signaling 4 (RGS4) as a novel target for GATA-6 transcription factor. Although three sites (a, b, c) within the proximal region of rabbit RGS4 promoter for GATA transcription factors were predicted by bioinformatics analysis, only GATA-a site (16 bp from the core TATA box) is essential for RGS4 transcriptional regulation. RT-PCR analysis demonstrated that only GATA-6 was highly expressed in rabbit colonic smooth muscle cells but GATA-4/6 were expressed in cardiac myocytes and GATA-1/2/3 expressed in blood cells. Adenovirus-mediated expression of GATA-6 but not GATA-1 significantly increased the constitutive and IL-1β-induced mRNA expression of the endogenous RGS4 in colonic smooth muscle cells. IL-1β stimulation induced GATA-6 nuclear translocation and increased GATA-6 binding to RGS4 promoter. These data suggest that GATA factor could affect G protein signaling through regulating RGS4 expression, and GATA signaling may develop as a future therapeutic target for RGS4-related diseases.
authors.affiliation: Department of Neuroscience, Temple University Lewis Katz School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neuroscience, Temple University Lewis Katz School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Neuroscience, Temple University Lewis Katz School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Physiology and Biophysics, Medical College of Virginia Campus, Virginia Commonwealth University, 1101 East Marshall Street, Richmond, VA 23298, USA.
authors.forename: Wu
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Neuroscience, Temple University Lewis Katz School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Chaoran
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Neuroscience, Temple University Lewis Katz School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Biophysics, Medical College of Virginia Campus, Virginia Commonwealth University, 1101 East Marshall Street, Richmond, VA 23298, USA.
authors.forename: Karnam S
authors.initials: KS
authors.lastname: Murthy
authors.affiliation: Department of Neuroscience, Temple University Lewis Katz School of Medicine, 3500 N Broad Street, Philadelphia, PA 19140, USA. Electronic address: whu@temple.edu.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Hu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D016297:Mutagenesis, Site-Directed; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction
chemical_list: D050982:GATA1 Transcription Factor; D050993:GATA6 Transcription Factor; D053583:Interleukin-1beta; D020710:RGS Proteins; D012333:RNA, Messenger; C098799:RGS4 protein
keywords: GATA transcription factors; Gastrointestinal tract; Gene regulations; Regulator of G protein signaling; Smooth muscle cells