Connections Between ETV6-Modulated Genes: Identification of Shared Features

Accumulating genetic and functional evidence point to ETV6 as being the tumour suppressor gene targeted by the deletions at chromosome 12p12-13 found in various cancers, particularly childhood leukemia. ETV6 is a ubiquitously expressed transcription factor (TF) of the ETS family with very few known...

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Main Authors: Daniel Sinnett, Jasmine Healy, Gino Boily, Patrick Beaulieu
Format: Article
Language:English
Published: SAGE Publishing 2008-01-01
Series:Cancer Informatics
Subjects:
Online Access:http://la-press.com/article.php?article_id=727
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author Daniel Sinnett
Jasmine Healy
Gino Boily
Patrick Beaulieu
author_facet Daniel Sinnett
Jasmine Healy
Gino Boily
Patrick Beaulieu
author_sort Daniel Sinnett
collection DOAJ
description Accumulating genetic and functional evidence point to ETV6 as being the tumour suppressor gene targeted by the deletions at chromosome 12p12-13 found in various cancers, particularly childhood leukemia. ETV6 is a ubiquitously expressed transcription factor (TF) of the ETS family with very few known targeted genes. We recently compiled a list of 87 ETV6-modulated genes that can be classified into a number of subgroups based on their coordinated expression patterns. In the present report, we hypothesized that genes presenting a similar profile of modulation could also share biological features, promoter sequence similarities and/or, common transcription factor binding sites (TFBSs). Using an exploratory approach based on hierarchical clustering of expression data, Gene Ontology (GO) terms, sequence similarity and evolutionary conserved putative TFBSs, we found that many genes presenting a similar expression profile also share biological features and/or conserved predicted TFBSs but rarely show detectable promoter sequence similarities. We also calculated the proportion of ETV6-modulated genes that have any conserved TFBSs of the Jaspar database in their regulatory sequence and compared these proportions to those calculated for two other gene lists, ETV6 non-modulated and ETS-regulated. We found that the NF-kB, c-REL and p65 TFBSs, which all bind TFs of the REL class, were under-represented among the ETV6-modulated genes compared to the ETV6-non-modulated genes, while the Broad-complex 1 TFBS appeared to be over-represented. NF-Y and Chop/cEBP TFBSs were over-represented in the promoters of ETV6-modulated genes compared to ETS-regulated genes. These analyses will help direct further studies intending to understand the role of ETV6 as a transcriptional regulator and aid in constructing the ETV6-regulatory gene network.
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spelling doaj.art-fedad9bdb26a405abcc5280b8834f52c2022-12-22T01:07:37ZengSAGE PublishingCancer Informatics1176-93512008-01-016183201Connections Between ETV6-Modulated Genes: Identification of Shared FeaturesDaniel SinnettJasmine HealyGino BoilyPatrick BeaulieuAccumulating genetic and functional evidence point to ETV6 as being the tumour suppressor gene targeted by the deletions at chromosome 12p12-13 found in various cancers, particularly childhood leukemia. ETV6 is a ubiquitously expressed transcription factor (TF) of the ETS family with very few known targeted genes. We recently compiled a list of 87 ETV6-modulated genes that can be classified into a number of subgroups based on their coordinated expression patterns. In the present report, we hypothesized that genes presenting a similar profile of modulation could also share biological features, promoter sequence similarities and/or, common transcription factor binding sites (TFBSs). Using an exploratory approach based on hierarchical clustering of expression data, Gene Ontology (GO) terms, sequence similarity and evolutionary conserved putative TFBSs, we found that many genes presenting a similar expression profile also share biological features and/or conserved predicted TFBSs but rarely show detectable promoter sequence similarities. We also calculated the proportion of ETV6-modulated genes that have any conserved TFBSs of the Jaspar database in their regulatory sequence and compared these proportions to those calculated for two other gene lists, ETV6 non-modulated and ETS-regulated. We found that the NF-kB, c-REL and p65 TFBSs, which all bind TFs of the REL class, were under-represented among the ETV6-modulated genes compared to the ETV6-non-modulated genes, while the Broad-complex 1 TFBS appeared to be over-represented. NF-Y and Chop/cEBP TFBSs were over-represented in the promoters of ETV6-modulated genes compared to ETS-regulated genes. These analyses will help direct further studies intending to understand the role of ETV6 as a transcriptional regulator and aid in constructing the ETV6-regulatory gene network.http://la-press.com/article.php?article_id=727ETV6ets membertranscription factormicroarraysleukemogenesis
spellingShingle Daniel Sinnett
Jasmine Healy
Gino Boily
Patrick Beaulieu
Connections Between ETV6-Modulated Genes: Identification of Shared Features
Cancer Informatics
ETV6
ets member
transcription factor
microarrays
leukemogenesis
title Connections Between ETV6-Modulated Genes: Identification of Shared Features
title_full Connections Between ETV6-Modulated Genes: Identification of Shared Features
title_fullStr Connections Between ETV6-Modulated Genes: Identification of Shared Features
title_full_unstemmed Connections Between ETV6-Modulated Genes: Identification of Shared Features
title_short Connections Between ETV6-Modulated Genes: Identification of Shared Features
title_sort connections between etv6 modulated genes identification of shared features
topic ETV6
ets member
transcription factor
microarrays
leukemogenesis
url http://la-press.com/article.php?article_id=727
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AT jasminehealy connectionsbetweenetv6modulatedgenesidentificationofsharedfeatures
AT ginoboily connectionsbetweenetv6modulatedgenesidentificationofsharedfeatures
AT patrickbeaulieu connectionsbetweenetv6modulatedgenesidentificationofsharedfeatures