Role of transcription factor Sp1 and CpG methylation on the regulation of the human podocalyxin gene promoter

Butta, Nora; Larrucea, Susana; Alonso, Sonia Conde; Rodríguez, Ramón B.; Arias-Salgado, Elena G; Ayuso, Matilde Sánchez; González-Manchón, Consuelo; Parrilla, Roberto L.

doi:10.1186/1471-2199-7-17

Cited by 44 publications

(21 citation statements)

References 33 publications

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“…6 A ). It has been reported that cytosine methylation may inhibit Sp1 binding to its consensus sites, therefore affecting its positive trans -activity (38, 39). Thus, we asked whether this epigenetic modification might play a role in the modulation of Sp1 binding to the SYN1 promoter.…”

Section: Resultsmentioning

confidence: 99%

Specificity Protein 1 (Sp1)-dependent Activation of the Synapsin I Gene (SYN1) Is Modulated by RE1-silencing Transcription Factor (REST) and 5′-Cytosine-Phosphoguanine (CpG) Methylation

Paonessa

Latifi

Scarongella

et al. 2013

Journal of Biological Chemistry

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Background: Syn I plays a key role at presynaptic terminals.Results: Sp1 binds to the SYN1 promoter, activating its transcription.Conclusion: Sp1 is a novel regulator of SYN1 transcription, whose activity is inhibited by REST and CpG methylation.Significance: Elucidating the mechanisms underlying basal activation of neuron-specific genes is fundamental to understand brain pathologies, where transcription is often dysregulated.

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Section: Resultsmentioning

confidence: 99%

Specificity Protein 1 (Sp1)-dependent Activation of the Synapsin I Gene (SYN1) Is Modulated by RE1-silencing Transcription Factor (REST) and 5′-Cytosine-Phosphoguanine (CpG) Methylation

Paonessa

Latifi

Scarongella

et al. 2013

Journal of Biological Chemistry

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“…On the other hand, Sp1, which also plays a role in podocyte differentiation [24,25,26], was shown to specifically bind reg3 in EMSA supershift experiments (fig. 4a).…”

Section: Discussionmentioning

confidence: 99%

“…Sp1 is ubiquitously expressed, but notably there are up to 100-fold differences in the levels of Sp1 in different cell types of the developing mouse embryo, which may reflect involvement in cell-specific transcription regulation pathways [24]. A role for this transcription factor in nephrogenesis has been proposed based on data for its spatial and temporal expression in developing glomeruli and its ability to regulate WT1 and podx1 expression [25,26]. …”

Section: Introductionmentioning

confidence: 99%

Sp1 Specifically Binds to an Evolutionarily Conserved DNA Segment within a Region Necessary for Podocyte-Specific Expression of Nephrin

Beltcheva

Hjörleifsdóttir

Kontusaari

et al. 2009

Nephron Exp Nephrol

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We have analyzed a conserved 237-bp segment located in a 1.9-kb upstream region of the nephrin gene, previously shown to contain kidney specific enhancer element(s). Electromobility shift assay was used to identify a 20-nucleotide region specifically recognized and bound by protein factors in nuclear extracts from immortalized podocyte and human embryonic kidney cell lines. The region was further narrowed down by competition assays to a stretch of 6 consecutive guanines, which are conserved at this location in multiple species. Introduction of mutations in this sequence abolished all protein binding activity whereas mutations in the flanking nucleotides did not. By means of gel supershift and chromatin immunoprecipitation assays we have shown that the protein factor from podocyte nuclear extracts able to recognize and bind the target sequence is the Sp1 zinc-finger protein.

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“…Some studies have found that methylation of SP1 binding sites prevents its binding and subsequent gene activation, while others have shown that methylation of SP1 binding sites does not alter its binding (e.g. Harrington et al, 1988; Holler et al, 1988; Mancini et al, 1999; Butta et al, 2006; Douet et al, 2007). We found that there were no obvious differences in the DNA methylation patterns associated with the SP1 binding sites between the Pit-1/0 cell lines, which do not express the Lhx3 gene and the Pit-1/Triple cell line that does express the Lhx3 gene.…”

Section: Discussionmentioning

confidence: 99%

The role of DNA methylation in regulation of the murine Lhx3 gene

Malik¹,

Rhodes²

2014

Gene

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LHX3 is a LIM-homeodomain transcription factor with critical roles in pituitary and nervous system development. Mutations in the LHX3 gene are associated with pediatric diseases featuring severe hormone deficiencies, hearing loss, developmental delay, and other symptoms. The mechanisms that govern LHX3/Lhx3 transcription are poorly understood. In this study, we examined the role of DNA methylation in the expression status of the mouse Lhx3 gene. Pituitary cells that do not normally express Lhx3 (Pit-1/0 cells) were treated with 5-aza-2’-deoxycytidine, a demethylating reagent. This treatment lead to activation of Lhx3 gene expression suggesting that methylation contributes to Lhx3 regulation. Treatment of Pit-1/0 pituitary cells with a combination of a demethylating reagent and a histone deacetylase inhibitor led to rapid activation of Lhx3 expression, suggesting possible crosstalk between DNA methylation and histone modification processes. To assess DNA methylation levels, treated and untreated Pit-1/0 genomic DNA was subjected to bisulfite conversion and sequencing. Treated Pit-1/0 cells had decreased methylation at specific sites in the Lhx3 locus compared to untreated cells. Chromatin immunoprecipitation assays demonstrated interactions between the MeCp2 methyl binding protein and Lhx3 promoter regions in the Pit-1/0 cell line. Overall, this study demonstrates that DNA methylation patterns of the Lhx3 gene are associated with its expression status.

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Role of transcription factor Sp1 and CpG methylation on the regulation of the human podocalyxin gene promoter

Cited by 44 publications

References 33 publications

Specificity Protein 1 (Sp1)-dependent Activation of the Synapsin I Gene (SYN1) Is Modulated by RE1-silencing Transcription Factor (REST) and 5′-Cytosine-Phosphoguanine (CpG) Methylation

Specificity Protein 1 (Sp1)-dependent Activation of the Synapsin I Gene (SYN1) Is Modulated by RE1-silencing Transcription Factor (REST) and 5′-Cytosine-Phosphoguanine (CpG) Methylation

Sp1 Specifically Binds to an Evolutionarily Conserved DNA Segment within a Region Necessary for Podocyte-Specific Expression of Nephrin

The role of DNA methylation in regulation of the murine Lhx3 gene

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