Mitochondria-localized glutamic acid-rich protein (MGARP) gene transcription is regulated by Sp1.

BACKGROUND:Mitochondria-localized glutamic acid-rich protein is a novel mitochondrial transmembrane protein expressed mainly in steroidogenic tissues and in the visual system. Previous studies showed that functions in hormone biosynthesis and its expression is modulated by the HPG axis. METHODOLOGY/PRINCIPAL FINDINGS:By bioinformatics, we identified two characteristic GC-rich motifs that are located proximal to the transcription start site (TSS) of and each contains two Specificity protein 1 (Sp1) binding elements. We then determined that the -3 kb proximal MGduanyu37 promoter is activated in a Sp1-dependent manner using reporter assays and knockdown of Sp1 led to decreased expression of endogenous MGduanyu37 messages. We also demonstrated that one of the two GC-rich motifs, GC-Box1, harbors prominent promoter activity mediated by Sp1, and that it requires both GC boxes for full transcriptional activation. These findings suggest a dominant role for these GC boxes and Sp1 in activating the MGduanyu37 promoter through a synergistic mechanism. Consistently, the results of an Electrophoretic Mobility Gel Shift Assay (EMSA) and Chromatin Immunoprecipitation (ChIP) confirmed that Sp1 specifically interacts with the GC-rich region. We further found that estrogen receptor α (ERα), a known Sp1 co-activator, could potentiate GC-boxes containing MGduanyu37 promoter activity and this effect is mediated by Sp1. Knockdown of Sp1 significantly diminished the MGduanyu37 promoter transactivation and the expression of endogenous MGduanyu37 mediated by both Sp1 and ERα. CONCLUSIONS/SIGNIFICANCE:The present study identified a proximal core sequence in the MGduanyu37 promoter that is composed of two enriched Sp1 binding motifs and established Sp1 as one major MGduanyu37 transactivator whose functions are synergistic with ERα, providing a novel understanding of the mechanisms of MGduanyu37 gene transcriptional regulation.

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