Johnson, R, Gamblin, RJ, Ooi, L et al. (6 more authors) (2006) Identification of the REST regulon reveals extensive transposable element-mediated binding site duplication. Nucleic Acids Research, 34 (14). pp. 3862-3877. ISSN 0305-1048
Abstract
The genome-wide mapping of gene-regulatory motifs remains a major goal that will facilitate the modelling of gene-regulatory networks and their evolution. The repressor element 1 is a long, conserved transcription factor-binding site which recruits the transcriptional repressor REST to numerous neuron-specific target genes. REST plays important roles in multiple biological processes and disease states. To map RE1 sites and target genes, we created a position specific scoring matrix representing the RE1 and used it to search the human and mouse genomes. We identified 1301 and 997 RE1s inhuman and mouse genomes, respectively, of which >40% are novel. By employing an ontological analysis we show that REST target genes are significantly enriched in a number of functional classes. Taking the novel REST target gene CACNA1A as an experimental model, we show that it can be regulated by multiple RE1s of different binding affinities, which are only partially conserved between human and mouse. A novel BLAST methodology indicated that many RE1s belong to closely related families. Most of these sequences are associated with transposable elements, leading us to propose that transposon-mediated duplication and insertion of RE1s has led to the acquisition of novel target genes by REST during evolution.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2006, The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | transcription factor; in-vivo; GENE-EXPRESSION; target genes; RESTRICTIVE SILENCER FACTOR; GENOME-WIDE ANALYSIS; NEURONAL GENES; REGULATORY REGIONS; CACNA1A GENE; CHANNEL GENE |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 12 Jul 2016 15:11 |
Last Modified: | 21 Nov 2018 13:56 |
Published Version: | http://dx.doi.org/10.1093/nar/gkl525 |
Status: | Published |
Publisher: | Oxford University Press, Academic Division |
Identification Number: | 10.1093/nar/gkl525 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:94389 |