Mapping of Human FOXP2 Enhancers Reveals Complex Regulation
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...
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2018-02-01
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doaj-e4f01b4e5f4545c8a7bd6d90e6721dd82020-11-24T21:33:00ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-02-011110.3389/fnmol.2018.00047312964Mapping of Human FOXP2 Enhancers Reveals Complex RegulationMartin Becker0Martin Becker1Paolo Devanna2Simon E. Fisher3Simon E. Fisher4Sonja C. Vernes5Sonja C. Vernes6Neurogenetics of Vocal Communication Group, Max Planck Institute for Psycholinguistics, Nijmegen, NetherlandsLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, NetherlandsNeurogenetics of Vocal Communication Group, Max Planck Institute for Psycholinguistics, Nijmegen, NetherlandsLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, NetherlandsDonders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, NetherlandsNeurogenetics of Vocal Communication Group, Max Planck Institute for Psycholinguistics, Nijmegen, NetherlandsDonders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, NetherlandsMutations 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.http://journal.frontiersin.org/article/10.3389/fnmol.2018.00047/fullFOXP2enhancer elementsGeneticregulation of gene expressionlanguagelanguage disorders |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Martin Becker Martin Becker Paolo Devanna Simon E. Fisher Simon E. Fisher Sonja C. Vernes Sonja C. Vernes |
spellingShingle |
Martin Becker Martin Becker Paolo Devanna Simon E. Fisher Simon E. Fisher Sonja C. Vernes Sonja C. Vernes Mapping of Human FOXP2 Enhancers Reveals Complex Regulation Frontiers in Molecular Neuroscience FOXP2 enhancer elements Genetic regulation of gene expression language language disorders |
author_facet |
Martin Becker Martin Becker Paolo Devanna Simon E. Fisher Simon E. Fisher Sonja C. Vernes Sonja C. Vernes |
author_sort |
Martin Becker |
title |
Mapping of Human FOXP2 Enhancers Reveals Complex Regulation |
title_short |
Mapping of Human FOXP2 Enhancers Reveals Complex Regulation |
title_full |
Mapping of Human FOXP2 Enhancers Reveals Complex Regulation |
title_fullStr |
Mapping of Human FOXP2 Enhancers Reveals Complex Regulation |
title_full_unstemmed |
Mapping of Human FOXP2 Enhancers Reveals Complex Regulation |
title_sort |
mapping of human foxp2 enhancers reveals complex regulation |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2018-02-01 |
description |
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. |
topic |
FOXP2 enhancer elements Genetic regulation of gene expression language language disorders |
url |
http://journal.frontiersin.org/article/10.3389/fnmol.2018.00047/full |
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