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Molecular characterization of senescence marker protein-30 gene promoter: identification of repressor elements and functional nuclear factor binding sites.

ABSTRACT: BACKGROUND: Senescence marker protein-30 (SMP30), whose expression declines during aging in rat liver, has been proposed as an important aging marker. Besides apoptosis, SMP30 also protects cells against various other injuries by enhancement of membrane calcium-pump activity. The mechanism of this differential gene expression mechanism is not known. DNA-protein interactions, mutation analysis and luciferase reporter assay studies have been performed to elucidate the mechanism of transcriptional regulation of SMP30 gene. RESULTS: We have characterized up to -2750 bp of the promoter by DNA-protein interactions studies. Twenty eight transcription factor binding sites have been identified by DNase I footprinting and electrophoretic mobility shift assay (EMSA). Transient transfection of 5' and 3' -deleted promoter-reporter constructs and luciferase assay illustrated the region between -128/+157 bp is sufficient to drive promoter activity. We have mapped an essential regulatory region between -513 to -352 bp which causes a drastic decline of reporter activity. This region contains CdxA, GATA2 and SRY transcription factor binding sites. Individual mutation of these three sites showed increase in reporter activity. Mutation in SRY site (-403/-368) showed maximum increase in reporter activity among these three sites. Therefore, we suggest that SRY like protein may be acting as a strong repressor of SMP30 gene along with CdxA and GATA-2. We also report that mutation of both Sp1 (172/-148 bp) and a C/EBPbeta (-190/-177 bp) transcription binding site located adjacent to each other on SMP30 gene promoter, causes a significant enhancement in reporter activity than individual mutation, thus may be causing the repression of SMP30 promoter activity. CONCLUSION: These studies provide novel insights into the mechanism that regulate SMP30 gene expression.

SUBMITTER: Rath B

PROVIDER: S-EPMC2386801 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Molecular characterization of senescence marker protein-30 gene promoter: identification of repressor elements and functional nuclear factor binding sites.

Rath Bandita B Pandey Ravi S RS Debata Priya R PR Maruyama Naoki N Supakar Prakash C PC

BMC molecular biology 20080429

<h4>Background</h4>Senescence marker protein-30 (SMP30), whose expression declines during aging in rat liver, has been proposed as an important aging marker. Besides apoptosis, SMP30 also protects cells against various other injuries by enhancement of membrane calcium-pump activity. The mechanism of this differential gene expression mechanism is not known. DNA-protein interactions, mutation analysis and luciferase reporter assay studies have been performed to elucidate the mechanism of transcrip ...[more]

PMID: 18442420

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Project description:Transposable elements are powerful agents of evolution that can diversify transcriptional programs by distributing transcription factor DNA-binding sites throughout genomes. To investigate the extent that transposable elements provide transcription factor-binding motifs in Caenorhabditis elegans, we determined the genomic positions of DNA-binding motifs for 201 different transcription factors. Surprisingly, we found that almost all examined transcription factors have binding motifs that reside within transposable elements, and all types of transposable elements have at least 1 instance of a transcription factor motif, demonstrating that transposable elements provide previously unappreciated numbers of transcription factor-binding motifs to the C. elegans genome. After determining the occurrence of transcription factor motifs in transposable elements relative to the rest of the genome, we identified DNA-binding motifs for 45 different transcription factors that are greater than 20-fold enriched within transposable elements compared to what would be expected by chance. Consistent with potential functional roles for these transposable element-enriched transcription factor-binding sequences, we determined that all transcription factor motif types found in transposable elements have instances of residing within accessible chromatin sites associated with transcription factor binding. The overwhelming majority of transcription factor-binding motifs located within transposable elements associate with their cognate transcription factors, suggesting extensive binding of transcription factors to sequences within transposable elements. In addition, transposable elements with accessible or transcription factor-bound motifs reside in the putative promoter regions of approximately 12% of all protein-coding genes, providing widespread possibilities for influencing gene expression. This work represents the first comprehensive analysis of transposable element-transcription factor interactions in C. elegans and demonstrates that transposable element-provided transcription factor-binding sites are prevalent in this important model organism.

Dataset Information

Molecular characterization of senescence marker protein-30 gene promoter: identification of repressor elements and functional nuclear factor binding sites.

Publications

Molecular characterization of senescence marker protein-30 gene promoter: identification of repressor elements and functional nuclear factor binding sites.

Similar Datasets

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