TY - JOUR
T1 - Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex
AU - Perzel Mandell, Kira A.
AU - Price, Amanda J.
AU - Wilton, Richard
AU - Collado-Torres, Leonardo
AU - Tao, Ran
AU - Eagles, Nicholas J.
AU - Szalay, Alexander S.
AU - Hyde, Thomas
AU - Weinberger, Daniel R.
AU - Kleinman, Joel E.
AU - Jaffe, Andrew
N1 - Publisher Copyright:
© 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020
Y1 - 2020
N2 - DNA methylation (DNAm) is a key epigenetic regulator of gene expression across development. The developing prenatal brain is a highly dynamic tissue, but our understanding of key drivers of epigenetic variability across development is limited. We, therefore, assessed genomic methylation at over 39 million sites in the prenatal cortex using whole-genome bisulfite sequencing and found loci and regions in which methylation levels are dynamic across development. We saw that DNAm at these loci was associated with nearby gene expression and enriched for enhancer chromatin states in prenatal brain tissue. Additionally, these loci were enriched for genes associated with neuropsychiatric disorders and genes involved with neurogenesis. We also found autosomal differences in DNAm between the sexes during prenatal development, though these have less clear functional consequences. We lastly confirmed that the dynamic methylation at this critical period is specifically CpG methylation, with generally low levels of CpH methylation. Our findings provide detailed insight into prenatal brain development as well as clues to the pathogenesis of psychiatric traits seen later in life.
AB - DNA methylation (DNAm) is a key epigenetic regulator of gene expression across development. The developing prenatal brain is a highly dynamic tissue, but our understanding of key drivers of epigenetic variability across development is limited. We, therefore, assessed genomic methylation at over 39 million sites in the prenatal cortex using whole-genome bisulfite sequencing and found loci and regions in which methylation levels are dynamic across development. We saw that DNAm at these loci was associated with nearby gene expression and enriched for enhancer chromatin states in prenatal brain tissue. Additionally, these loci were enriched for genes associated with neuropsychiatric disorders and genes involved with neurogenesis. We also found autosomal differences in DNAm between the sexes during prenatal development, though these have less clear functional consequences. We lastly confirmed that the dynamic methylation at this critical period is specifically CpG methylation, with generally low levels of CpH methylation. Our findings provide detailed insight into prenatal brain development as well as clues to the pathogenesis of psychiatric traits seen later in life.
KW - DNA methylation
KW - brain development
KW - prenatal development
KW - whole-genome bisulfite sequencing
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U2 - 10.1080/15592294.2020.1786304
DO - 10.1080/15592294.2020.1786304
M3 - Article
C2 - 32602773
AN - SCOPUS:85084420813
SN - 1559-2294
SP - 1
EP - 13
JO - Epigenetics
JF - Epigenetics
ER -