Original Research ARTICLE
Mapping of human FOXP2 enhancers reveals complex regulation
- 1Neurogenetics of Vocal Communication Group, Max Planck Institute for Psycholinguistics (MPG), Netherlands
- 2Donders Institute for Brain, Cognition and Behaviour, Radboud University, Netherlands
- 3Language and Genetics Department, Max Planck Institute for Psycholinguistics (MPG), Netherlands
- 4Current address: Department of Women’s and Children’s Health, Karolinska Institute (KI), Sweden
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 temporal-spatial 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.
Keywords: FoxP2, Enhancer Elements, Genetic, regulation of gene expression, Language, Language Disorders, Tbr1
Received: 23 Oct 2017;
Accepted: 02 Feb 2018.
Edited by:Ildikó Rácz, Universitätsklinikum Bonn, Germany
Reviewed by:Nenad Sestan, Yale School of Medicine, Yale University, United States
Ozgun Gokce, Ludwig-Maximilians-Universität München, Germany
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.
* Correspondence: Dr. Sonja C. Vernes, Max Planck Institute for Psycholinguistics (MPG), Neurogenetics of Vocal Communication Group, Wundlaan 1, Nijmegen, 6525XD, Netherlands, email@example.com