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Dual role of C/ EBP α as an activator and repressor of Gα i2 gene transcription
Author(s) -
Xu Jinxian,
Kawai Yumiko,
Arinze Ifeanyi J.
Publication year - 2013
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12102
Subject(s) - repressor , microbiology and biotechnology , activator (genetics) , biology , promoter , transcription (linguistics) , ccaat enhancer binding proteins , gene expression , sp1 transcription factor , transcription factor , sodium butyrate , gene , regulation of gene expression , response element , creb , butyrate , transcriptional regulation , dna binding protein , biochemistry , linguistics , philosophy , fermentation
The G‐protein Gα i2 mediates signaling in a variety of processes. Induced expression of Gα i2 by butyrate and various transcription factors has been established, but transcriptional suppression has not previously been explored. Using HepG2 and K562 cells in culture, we show here that whereas both C/ EBP α and C/ EBP β induced transcription from the Gα i2 gene promoter, C/ EBP α, but not C/ EBP β, inhibited butyrate‐induced Gα i2 expression. Because the transcriptional effect of butyrate on this gene promoter is largely mediated by the transcription factor Sp1, we investigated whether C/ EBP α influenced Sp1‐induced Gα i2 gene transcription. Binding of C/ EBP α to a C/ EBP response element in Gα i2 gene promoter inhibited Sp1‐induced promoter activity. Ch IP analysis showed decreased butyrate‐induced recruitment of Sp1 to the Gα i2 gene promoter in response to C/ EBP α treatment. Incubating cells with acetate or transfecting them with expression plasmid for either the acetyltransferase p300 or CREB‐binding protein ( CBP ) reversed the antagonistic effect of C/ EBP α on Sp1‐dependent gene transcription, suggesting that the mechanistic basis for the antagonism is related to the squelching of co‐activator acetyltransferase(s) by C/ EBP α or the acetylation of Sp1 and/or C/ EBP α. This work reveals that C/ EBP α plays a dual role as an activator and as a repressor of Gα i2 gene transcription.