Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes
<p>Abstract</p> <p>Background</p> <p>Different approaches have been developed to dissect the interplay between transcription factors (TFs) and their cis-acting sequences on DNA in order to identify TF target genes. Here we used a combination of computational and experim...
| Main Authors: | , , , , , |
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| Format: | Article |
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BMC
2010-06-01
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| Series: | BMC Genomics |
| Online Access: | http://www.biomedcentral.com/1471-2164/11/355 |
| _version_ | 1818485276833480704 |
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| author | Ubezio Benedetta Corà Davide Orso Francesca Provero Paolo Caselle Michele Taverna Daniela |
| author_facet | Ubezio Benedetta Corà Davide Orso Francesca Provero Paolo Caselle Michele Taverna Daniela |
| author_sort | Ubezio Benedetta |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Different approaches have been developed to dissect the interplay between transcription factors (TFs) and their cis-acting sequences on DNA in order to identify TF target genes. Here we used a combination of computational and experimental approaches to identify novel direct targets of TFAP2A, a key TF for a variety of physiological and pathological cellular processes. Gene expression profiles of HeLa cells either silenced for TFAP2A by RNA interference or not were previously compared and a set of differentially expressed genes was revealed.</p> <p>Results</p> <p>The regulatory regions of 494 TFAP2A-modulated genes were analyzed for the presence of TFAP2A binding sites, employing the canonical TFAP2A Positional Weight Matrix (PWM) reported in Jaspar <url>http://jaspar.genereg.net/</url>. 264 genes containing at least 2 high score TFAP2A binding sites were identified, showing a central role in "Cellular Movement" and "Cellular Development". In an attempt to identify TFs that could cooperate with TFAP2A, a statistically significant enrichment for SP1 binding sites was found for TFAP2A-activated but not repressed genes. The direct binding of TFAP2A or SP1 to a random subset of TFAP2A-modulated genes was demonstrated by Chromatin ImmunoPrecipitation (ChIP) assay and the TFAP2A-driven regulation of DCBLD2/ESDN/CLCP1 gene studied in details.</p> <p>Conclusions</p> <p>We proved that our computational approaches applied to microarray selected genes are valid tools to identify functional TF binding sites in gene regulatory regions as confirmed by experimental validations. In addition, we demonstrated a fine-tuned regulation of DCBLD2/ESDN transcription by TFAP2A.</p> |
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| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-10T16:06:30Z |
| publishDate | 2010-06-01 |
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| series | BMC Genomics |
| spelling | doaj.art-833b5898ee744abca4c1c6e9ea381cb32022-12-22T01:42:13ZengBMCBMC Genomics1471-21642010-06-0111135510.1186/1471-2164-11-355Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genesUbezio BenedettaCorà DavideOrso FrancescaProvero PaoloCaselle MicheleTaverna Daniela<p>Abstract</p> <p>Background</p> <p>Different approaches have been developed to dissect the interplay between transcription factors (TFs) and their cis-acting sequences on DNA in order to identify TF target genes. Here we used a combination of computational and experimental approaches to identify novel direct targets of TFAP2A, a key TF for a variety of physiological and pathological cellular processes. Gene expression profiles of HeLa cells either silenced for TFAP2A by RNA interference or not were previously compared and a set of differentially expressed genes was revealed.</p> <p>Results</p> <p>The regulatory regions of 494 TFAP2A-modulated genes were analyzed for the presence of TFAP2A binding sites, employing the canonical TFAP2A Positional Weight Matrix (PWM) reported in Jaspar <url>http://jaspar.genereg.net/</url>. 264 genes containing at least 2 high score TFAP2A binding sites were identified, showing a central role in "Cellular Movement" and "Cellular Development". In an attempt to identify TFs that could cooperate with TFAP2A, a statistically significant enrichment for SP1 binding sites was found for TFAP2A-activated but not repressed genes. The direct binding of TFAP2A or SP1 to a random subset of TFAP2A-modulated genes was demonstrated by Chromatin ImmunoPrecipitation (ChIP) assay and the TFAP2A-driven regulation of DCBLD2/ESDN/CLCP1 gene studied in details.</p> <p>Conclusions</p> <p>We proved that our computational approaches applied to microarray selected genes are valid tools to identify functional TF binding sites in gene regulatory regions as confirmed by experimental validations. In addition, we demonstrated a fine-tuned regulation of DCBLD2/ESDN transcription by TFAP2A.</p>http://www.biomedcentral.com/1471-2164/11/355 |
| spellingShingle | Ubezio Benedetta Corà Davide Orso Francesca Provero Paolo Caselle Michele Taverna Daniela Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes BMC Genomics |
| title | Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes |
| title_full | Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes |
| title_fullStr | Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes |
| title_full_unstemmed | Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes |
| title_short | Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes |
| title_sort | identification of functional tfap2a and sp1 binding sites in new tfap2a modulated genes |
| url | http://www.biomedcentral.com/1471-2164/11/355 |
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