Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex

Image credit: bioRxiv

Abstract

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.

Publication
Epigenetics
Leonardo Collado-Torres
Leonardo Collado-Torres
Investigator @ LIBD, Assistant Professor, Department of Biostatistics @ JHBSPH

#rstats @Bioconductor/🧠 genomics @LieberInstitute/@lcgunam @jhubiostat @jtleek @andrewejaffe alumni/@LIBDrstats @CDSBMexico co-founder

Nicholas J. Eagles
Nicholas J. Eagles
Research Assistant 2018-2021, Research Associate I 2021-2024, Research Associate II 2024-ongoing