Sp1 and Sp3 physically interact and co-operate with GABP for the activation of the utrophin promoter

Galvagni, Federico; Capo, Sabrina; Oliviero, Salvatore

doi:10.1006/jmbi.2000.4335

Cited by 67 publications

(48 citation statements)

References 66 publications

(98 reference statements)

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“…S10). SP1, YY1, and GABPA have been previously described as interacting partners (Galvagni et al 2001;Rosmarin et al 2004), and these pathway enrichments are consistent with previous studies implicating GABPA in controlling stem cell maintenance and differentiation (Yu et al 2016). …”

Section: Dap Binding Recapitulates Known Liver Expression Programssupporting

confidence: 90%

A genome-wide interactome of DNA-associated proteins in the human liver

et al. 2017

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Large-scale efforts like the ENCODE Project have made tremendous progress in cataloging the genomic binding patterns of DNA-associated proteins (DAPs), such as transcription factors (TFs). However, most chromatin immunoprecipitation-sequencing (ChIP-seq) analyses have focused on a few immortalized cell lines whose activities and physiology differ in important ways from endogenous cells and tissues. Consequently, binding data from primary human tissue are essential to improving our understanding of in vivo gene regulation. Here, we identify and analyze more than 440,000 binding sites using ChIP-seq data for 20 DAPs in two human liver tissue samples. We integrated binding data with transcriptome and phased WGS data to investigate allelic DAP interactions and the impact of heterozygous sequence variation on the expression of neighboring genes. Our tissue-based data set exhibits binding patterns more consistent with liver biology than cell lines, and we describe uses of these data to better prioritize impactful noncoding variation. Collectively, our rich data set offers novel insights into genome function in human liver tissue and provides a valuable resource for assessing disease-related disruptions.

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Section: Dap Binding Recapitulates Known Liver Expression Programssupporting

confidence: 90%

A genome-wide interactome of DNA-associated proteins in the human liver

et al. 2017

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“…When comparing our model systems, higher levels of GABP mRNA are associated with higher levels of steady state TSPO mRNA. GABP is also a target of c-Raf and JNK (49), and it physically interacts and cooperates with Sp1 and Sp3 for the activation of at least one promoter (50). Interestingly, absence of Ets1 mRNA is also associated with high levels of TSPO mRNA, an observation that is corroborated by the fact that induced downregulation of Ets1 in NIH/3T3 cells results in increased TSPO mRNA.…”

Section: Discussionmentioning

confidence: 94%

The Role of Ets Transcription Factors in the Basal Transcription of the Translocator Protein (18 kDa)

et al. 2007

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The translocator protein (18kDa; TSPO), previously known as peripheral-type benzodiazepine receptor, is a high affinity cholesterol-and drug-binding mitochondrial protein involved in various cell functions including steroidogenesis, apoptosis, and proliferation. TSPO is highly expressed in secretory and glandular tissues, especially in steroidogenic cells, and its expression is altered in certain pathological conditions such as cancer and neurological diseases. In this study, we characterized the regulatory elements present in the region of the TPSO promoter extending from 515 to 805-bp upstream of the transcription start site, an area previously identified as being important for transcription. Promoter fragments extending 2.7-kb and 805-bp upstream of the transcription start site were able to direct enhanced green fluorescent protein expression to Leydig cells of the testis, theca cells of the ovary, and cells of the adrenal cortex in transgenic animals. This expression pattern perfectly mimicked endogenous TSPO expression. Functional characterization of the 515 to 805-bp region revealed the presence of one Specificity protein 1/Specificity protein 3 (Sp1/Sp3) and two vets erythroblastosis virus E26 oncogene homolog (Ets) binding sites that are important for transcriptional activity in both MA-10 mouse Leydig tumor cells and NIH/3T3 whole mouse embryo fibroblasts. GA-binding protein α (GABPα) -a member of the Ets family of transcription factorswas found to be associated with the endogenous TSPO promoter. We conclude that Sp1/Sp3 and members of the Ets family of transcription factors bind to specific binding sites in the TSPO promoter to drive basal TSPO gene transcription.

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“…We and others (Gramolini et al, 1999a;Khurana et al, 1999) have shown that the nerve-derived growth factor heregulin (HRG) causes a N-box-mediated increase in utrophin-A promoter activity via extracellular signal-regulated kinase-dependent activation of the Ets-related transcription factor complex GABP␣/␤, in a manner similar to that noted in the nACHR␦ and nACHR subunit promoters (Falls et al, 1993;Koike et al, 1995;Sapru et al, 1998; This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06 -12-1069) on May 16, 2007. 1998). Additionally, SP1 (Galvagni et al, 2001;Gyrd-Hansen et al, 2002), NFATc1/calcineurin (Chakkalakal et al, 2003;Chakkalakal et al, 2004), and myogenic factors (Gramolini and Jasmin, 1999;Perkins et al, 2001) can also activate the utrophin-A promoter. Recently, the 5Ј-untranslated region of utrophin-A promoter has been shown to be important for regulation of utrophin protein levels during regeneration as well (Miura et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, SP1 (Galvagni et al, 2001;Gyrd-Hansen et al, 2002), NFATc1/calcineurin (Chakkalakal et al, 2003;Chakkalakal et al, 2004), and myogenic factors (Gramolini and Jasmin, 1999;Perkins et al, 2001) can also activate the utrophin-A promoter. Recently, the 5Ј-untranslated region of utrophin-A promoter has been shown to be important for regulation of utrophin protein levels during regeneration as well (Miura et al, 2005).…”

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confidence: 99%

Ets-2 Repressor Factor Silences Extrasynaptic Utrophin by N-Box–mediated Repression in Skeletal Muscle

Perkins

Basu

Budak

et al. 2007

MBoC

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Utrophin is the autosomal homologue of dystrophin, the protein product of the Duchenne's muscular dystrophy (DMD) locus. Utrophin expression is temporally and spatially regulated being developmentally down-regulated perinatally and enriched at neuromuscular junctions (NMJs) in adult muscle. Synaptic localization of utrophin occurs in part by heregulin-mediated extracellular signal-regulated kinase (ERK)-phosphorylation, leading to binding of GABP␣/␤ to the N-box/EBS and activation of the major utrophin promoter-A expressed in myofibers. However, molecular mechanisms contributing to concurrent extrasynaptic silencing that must occur to achieve NMJ localization are unknown. We demonstrate that the Ets-2 repressor factor (ERF) represses extrasynaptic utrophin-A in muscle. Gel shift and chromatin immunoprecipitation studies demonstrated physical association of ERF with the utrophin-A promoter N-box/EBS site. ERF overexpression repressed utrophin-A promoter activity; conversely, small interfering RNA-mediated ERF knockdown enhanced promoter activity as well as endogenous utrophin mRNA levels in cultured muscle cells in vitro. Laser-capture microscopy of tibialis anterior NMJ and extrasynaptic transcriptomes and gene transfer studies provide spatial and direct evidence, respectively, for ERF-mediated utrophin repression in vivo. Together, these studies suggest "repressing repressors" as a potential strategy for achieving utrophin up-regulation in DMD, and they provide a model for utrophin-A regulation in muscle. INTRODUCTIONDuchenne's muscular dystrophy (DMD) is a fatal neuromuscular disease caused by gene mutations leading to qualitative or quantitative disturbances in dystrophin expression (Hoffman et al., 1987). Dystrophin-related protein or utrophin is considered the autosomal homologue of dystrophin, because it shares extensive sequence homology as well as its size and abundance in muscle (Love et al., 1989;Khurana et al., 1990;Tinsley et al., 1992). Utrophin and dystrophin also share functional properties such as the ability to associate with the dystroglycan complex and bind F-actin (Matsumura et al., 1992;Winder and Kendrick, 1995;Rybakova et al., 2002). Direct evidence for the ability of utrophin to functionally substitute comes from experiments demonstrating that utrophin overexpression driven either by transgenic means Rafael et al., 1998;Tinsley et al., 1998;Fisher et al., 2001) or viral vectors (Gilbert et al., 1999;Wakefield et al., 2000;Cerletti et al., 2003) can rescue dystrophin-deficient muscle. Despite these functional similarities, dystrophin and utrophin exhibit distinct localization in normal adult tissues.Perinatally, utrophin is expressed throughout the sarcolemma, however, its expression declines as that of dystrophin increases (Khurana et al., 1991;Clerk et al., 1993), leading to its spatially restricted expression at neuromuscular and myotendinous junctions (NMJs and MTJs, respectively) of adult myofibers. These features and relevance toward a therapy for DMD provide a powerful impetus for b...

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Sp1 and Sp3 physically interact and co-operate with GABP for the activation of the utrophin promoter

Cited by 67 publications

References 66 publications

A genome-wide interactome of DNA-associated proteins in the human liver

A genome-wide interactome of DNA-associated proteins in the human liver

The Role of Ets Transcription Factors in the Basal Transcription of the Translocator Protein (18 kDa)

Ets-2 Repressor Factor Silences Extrasynaptic Utrophin by N-Box–mediated Repression in Skeletal Muscle

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