Chromatin Decondensation by FOXP2 Promotes Human Neuron Maturation and Expression of Neurodevelopmental Disease Genes

Stephanie L. Hickey, Stefano Berto, Genevieve Konopka

Research output: Contribution to journalArticle

Abstract

Forkhead box P2 (FOXP2)is a transcription factor expressed in the human brain that peaks during fetal development, and disruption in its ability to regulate downstream target genes leads to vulnerability to neurodevelopmental disorders. However, the mechanisms by which FOXP2 exerts regulatory control over targets during neuronal maturation have not been fully elucidated. Here, we use genome-wide chromatin accessibility assays and transcriptome-wide expression analyses in differentiating human neurons to show that FOXP2 represses proliferation-promoting genes in a DNA-binding-dependent manner. In contrast, FOXP2 and its cofactors, NFIA and NFIB, activate neuronal maturation genes in a manner that does not require FOXP2 to interact with DNA directly. Moreover, comparisons with expression data from the developing human brain suggest that FOXP2 and NFIA- or NFIB-dependent chromatin alterations drive maturation of excitatory cortical neurons. Thus, FOXP2 and its NFI cofactors may be specifically important for the development of cortical circuits underlying neurodevelopmental disorders.

Original languageEnglish (US)
Pages (from-to)1699-1711.e9
JournalCell Reports
Volume27
Issue number6
DOIs
StatePublished - May 7 2019

Fingerprint

Neurons
Chromatin
Genes
Brain
Aptitude
DNA
Fetal Development
Transcriptome
Transcription Factors
Genome
Assays
Networks (circuits)
Neurodevelopmental Disorders
Drive

Keywords

  • autism
  • cortex
  • language
  • neuron development
  • schizophrenia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chromatin Decondensation by FOXP2 Promotes Human Neuron Maturation and Expression of Neurodevelopmental Disease Genes. / Hickey, Stephanie L.; Berto, Stefano; Konopka, Genevieve.

In: Cell Reports, Vol. 27, No. 6, 07.05.2019, p. 1699-1711.e9.

Research output: Contribution to journalArticle

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