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...

Full description

Bibliographic Details
Main Authors: Martin Becker, Paolo Devanna, Simon E. Fisher, Sonja C. Vernes
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-02-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fnmol.2018.00047/full
id doaj-e4f01b4e5f4545c8a7bd6d90e6721dd8
record_format Article
spelling 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
work_keys_str_mv AT martinbecker mappingofhumanfoxp2enhancersrevealscomplexregulation
AT martinbecker mappingofhumanfoxp2enhancersrevealscomplexregulation
AT paolodevanna mappingofhumanfoxp2enhancersrevealscomplexregulation
AT simonefisher mappingofhumanfoxp2enhancersrevealscomplexregulation
AT simonefisher mappingofhumanfoxp2enhancersrevealscomplexregulation
AT sonjacvernes mappingofhumanfoxp2enhancersrevealscomplexregulation
AT sonjacvernes mappingofhumanfoxp2enhancersrevealscomplexregulation
_version_ 1725955274191142912