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.

Downregulation of thromboxane A2 and angiotensin II type 1 receptors associated with aging-related decrease in internal anal sphincter tone

“…There is substantial literature to suggest that the regulators of G-protein signaling (RGS), especially RGS2, GPCR kinase (GRK), and β-arrestin (Arrb), play an important role in regulating post-activation GPCR signaling 21,46,47 . Accordingly, GRKs phosphorylate agonist-activated GPCR and then Arrb bind to these phosphorylated GPCR, leading to receptor internalization and desensitization 48 .…”

<p>Association Analysis Between SNPs in the Promoter Region of <em>RGS4</em> and Schizophrenia in the Northern Chinese Han Population</p>

“…31 Transcription factors acting as critical activators or repressors regulate transcription by targeting cis-acting elements in the promoter region of genes. 32 RGS4 expression was regulated by some transcription factors, 33,34 such as C/EBP, Bcl6, 35 and GATA-6. 34 The SNPs identified in this study might affect the binding of specific transcription factors, leading to altered gene expression.…”

“…32 RGS4 expression was regulated by some transcription factors, 33,34 such as C/EBP, Bcl6, 35 and GATA-6. 34 The SNPs identified in this study might affect the binding of specific transcription factors, leading to altered gene expression. Functional assays are needed to address these possibilities.…”

Deep sequencing of the mouse lung transcriptome reveals distinct long non-coding RNAs expression associated with the high virulence of H5N1 avian influenza virus in mice

“…The GATA is a type of transcription factor that plays important roles in several diseases, such as haematopoietic, cardiovascular, gastrointestinal tract, liver and pancreas, urogenital tract and kidney, respiratory tract, mammary gland and central nervous system diseases[84]. Moreover, the GATA also directly affects G protein signaling through regulating the expression of regulator of G protein signaling 4 (RGS4)[85]. The transcription factor Myc involves in regulating the expression of miR-23b-27b cluster during hypoxia-induced neuronal apoptosis[86].…”