Mitochondria-localized glutamic acid-rich protein (MGARP) gene transcription is regulated by Sp1.
Mitochondria-localized glutamic acid-rich protein (MGARP) gene transcription is regulated by Sp1.
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DOI：
10.1371/journal.pone.0050053
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Jin D;Li R;Mao D;Luo N;Wang Y;Chen S;Zhang S
线粒体定位谷氨酸富蛋白（MGARP）是一种新型的线粒体跨膜蛋白，主要表达于类固醇组织和视觉系统。已有研究表明MGARP参与激素的生物合成，其表达受HPG轴调控。通过生物信息学，我们确定了两个特征的富含gc的基序，它们位于MGARP的转录起始位点（TSS）附近，每个基序都包含两个特异性蛋白1 （Sp1）结合元件。然后，我们确定- 3 kb的近端MGARP启动子以Sp1依赖的方式被激活，Sp1的敲除导致内源性MGARP信息的表达减少。我们还证明了两个富含GC的基序之一GC- box1具有由Sp1介导的显著启动子活性，并且需要两个GC盒才能完全激活转录。这些发现表明这些GC盒和Sp1通过协同机制在激活MGARP启动子中起主导作用。一致地，电泳迁移率凝胶位移测定（EMSA）和染色质免疫沉淀（ChIP）的结果证实Sp1特异性地与富含gc的区域相互作用。我们进一步发现雌激素受体α (ERα)，一种已知的Sp1共激活剂，可以增强含有MGARP启动子的gc -box活性，这种作用是由Sp1介导的。Sp1的敲低显著降低了MGARP启动子的反激活以及Sp1和ERα介导的内源性MGARP的表达。本研究确定了MGARP启动子的近端核心序列，该序列由两个富集的Sp1结合基序组成，并确定Sp1是一个主要的MGARP反激活子，其功能与ERα协同，为MGARP基因转录调控机制提供了新的认识。
Mitochondria-localized glutamic acid-rich protein (MGARP) is a novel mitochondrial transmembrane protein expressed mainly in steroidogenic tissues and in the visual system. Previous studies showed that MGARP functions in hormone biosynthesis and its expression is modulated by the HPG axis. By bioinformatics, we identified two characteristic GC-rich motifs that are located proximal to the transcription start site (TSS) of MGARP, and each contains two Specificity protein 1 (Sp1) binding elements. We then determined that the −3 kb proximal MGARP promoter is activated in a Sp1-dependent manner using reporter assays and knockdown of Sp1 led to decreased expression of endogenous MGARP 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 MGARP 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 MGARP promoter activity and this effect is mediated by Sp1. Knockdown of Sp1 significantly diminished the MGARP promoter transactivation and the expression of endogenous MGARP mediated by both Sp1 and ERα. The present study identified a proximal core sequence in the MGARP promoter that is composed of two enriched Sp1 binding motifs and established Sp1 as one major MGARP transactivator whose functions are synergistic with ERα, providing a novel understanding of the mechanisms of MGARP gene transcriptional regulation.
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DOI：
10.1083/jcb.200811033
发表时间：
2009-06-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Li Y;Lim S;Hoffman D;Aspenstrom P;Federoff HJ;Rempe DA
通讯作者：
Rempe DA
影响因子：
4.8
作者：
Khan, S;Abdelrahim, M;Safe, S
通讯作者：
Safe, S
影响因子：
4.3
作者：
Li, Yan;Rempe, David A.
通讯作者：
Rempe, David A.
影响因子：
4.8
作者：
Matsumoto, Tadashi;Minegishi, Kazuhiro;Yoshimura, Yasunori
通讯作者：
Yoshimura, Yasunori
影响因子：
64.5
作者：
COUREY, AJ;TJIAN, R
通讯作者：
TJIAN, R