@article{4f784569082d4e8bbed440843bb90198,
title = "Chromatin Decondensation by FOXP2 Promotes Human Neuron Maturation and Expression of Neurodevelopmental Disease Genes",
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.",
keywords = "autism, cortex, language, neuron development, schizophrenia",
author = "Hickey, {Stephanie L.} and Stefano Berto and Genevieve Konopka",
note = "Funding Information: We thank Drs. Joseph S. Takahashi, Jane E. Johnson, and Taekyung Kim for critical reading of the manuscript. We thank Marissa Co for providing constructs and editing the manuscript. We thank Drs. Arnold Kriegstein and Tomasz Nowakowski for providing the pseudotime and pseudodifferentiation data. G.K. is a Jon Heighten Scholar in Autism Research at UT Southwestern. This work was supported by the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition – Scholar Award and grants from the NIH (DC014702, DC016340, MH090238, MH102603, and MH107672)to G.K. S.L.H. performed all wet bench experiments, ATAC-seq bioinformatics, differential expression analysis, WGCNA, and comparisons with in vivo data. S.B. mapped and counted the RNA-seq reads and assisted with differential expression analysis. G.K. supervised the project, and S.L.H. S.B. and G.K. wrote the manuscript. The authors declare no competing interests. Funding Information: We thank Drs. Joseph S. Takahashi, Jane E. Johnson, and Taekyung Kim for critical reading of the manuscript. We thank Marissa Co for providing constructs and editing the manuscript. We thank Drs. Arnold Kriegstein and Tomasz Nowakowski for providing the pseudotime and pseudodifferentiation data. G.K. is a Jon Heighten Scholar in Autism Research at UT Southwestern. This work was supported by the James S. McDonnell Foundation 21 st Century Science Initiative in Understanding Human Cognition – Scholar Award and grants from the NIH ( DC014702 , DC016340 , MH090238 , MH102603 , and MH107672 ) to G.K. Funding Information: We thank Drs. Joseph S. Takahashi, Jane E. Johnson, and Taekyung Kim for critical reading of the manuscript. We thank Marissa Co for providing constructs and editing the manuscript. We thank Drs. Arnold Kriegstein and Tomasz Nowakowski for providing the pseudotime and pseudodifferentiation data. G.K. is a Jon Heighten Scholar in Autism Research at UT Southwestern. This work was supported by the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition – Scholar Award and grants from the NIH (DC014702, DC016340, MH090238, MH102603, and MH107672) to G.K. S.L.H. performed all wet bench experiments, ATAC-seq bioinformatics, differential expression analysis, WGCNA, and comparisons with in vivo data. S.B. mapped and counted the RNA-seq reads and assisted with differential expression analysis. G.K. supervised the project, and S.L.H. S.B. and G.K. wrote the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 The Author(s)",
year = "2019",
month = may,
day = "7",
doi = "10.1016/j.celrep.2019.04.044",
language = "English (US)",
volume = "27",
pages = "1699--1711.e9",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "6",
}