Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genesReport as inadecuate




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BMC Genomics

, 11:355

First Online: 03 June 2010Received: 01 March 2010Accepted: 03 June 2010

Abstract

BackgroundDifferent 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.

ResultsThe 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 http:-jaspar.genereg.net-. 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.

ConclusionsWe 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.

AbbreviationsTFstranscription factors

PWMPositional Weight Matrix

ChIPChromatin ImmunoPrecipitation

TFBSsTF Binding Sites

PFMPositional Frequency Matrix

TSSTranscriptional Start Site

GOGene Ontology

FCFold Change.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-11-355 contains supplementary material, which is available to authorized users.

Francesca Orso, Davide Corà, Michele Caselle and Daniela Taverna contributed equally to this work.

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Author: Francesca Orso - Davide Corà - Benedetta Ubezio - Paolo Provero - Michele Caselle - Daniela Taverna

Source: https://link.springer.com/article/10.1186/1471-2164-11-355



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