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Mapping of human FOXP2 enhancers reveals complex regulation

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Becker_2018_fMolNeuro_Mapping_human_FOXP2_CC.pdf (1.919Mb)
Date
21/02/2018
Author
Becker, Martin
Devanna, Paolo
Fisher, Simon E
Vernes, Sonja C
Keywords
FOXP2
Enhancer elements
Genetic
Regulation of gene expression
Language
Language disorders
TBR1
QH301 Biology
QH426 Genetics
DAS
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Abstract
Mutations of the FOXP2 gene cause a severe speech and language disorder, providing a molecular window into the neurobiology of language. Individuals with FOXP2 mutations have structural and functional alterations affecting brain circuits that overlap with sites of FOXP2 expression, including regions of the cortex, striatum, and cerebellum. FOXP2 displays complex patterns of expression in the brain, as well as in non-neuronal tissues, suggesting that sophisticated regulatory mechanisms control its spatio-temporal expression. However, to date, little is known about the regulation of FOXP2 or the genomic elements that control its expression. Using chromatin conformation capture (3C), we mapped the human FOXP2 locus to identify putative enhancer regions that engage in long-range interactions with the promoter of this gene. We demonstrate the ability of the identified enhancer regions to drive gene expression. We also show regulation of the FOXP2 promoter and enhancer regions by candidate regulators - FOXP family and TBR1 transcription factors. These data point to regulatory elements that may contribute to the temporal- or tissue-specific expression patterns of human FOXP2. Understanding the upstream regulatory pathways controlling FOXP2 expression will bring new insight into the molecular networks contributing to human language and related disorders.
Citation
Becker , M , Devanna , P , Fisher , S E & Vernes , S C 2018 , ' Mapping of human FOXP2 enhancers reveals complex regulation ' , Frontiers in Molecular Neuroscience , vol. 11 , 47 . https://doi.org/10.3389/fnmol.2018.00047
Publication
Frontiers in Molecular Neuroscience
Status
Peer reviewed
DOI
https://doi.org/10.3389/fnmol.2018.00047
ISSN
1662-5099
Type
Journal article
Rights
Copyright © 2018 Becker, Devanna, Fisher and Vernes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Description
Funding: This work was funded by the Max Planck Society. SCV was also supported by a Marie Curie Career Integration Grant (PCIG12-GA-2012-333978) and a Max Planck Independent Research Group Grant.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/21698

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