RT Journal Article
SR Electronic
T1 The methylome of the human frontal cortex across development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 005504
DO 10.1101/005504
A1 Andrew E. Jaffe
A1 Yuan Gao
A1 Ran Tao
A1 Thomas M. Hyde
A1 Daniel R. Weinberger
A1 Joel E. Kleinman
YR 2014
UL http://biorxiv.org/content/early/2014/05/27/005504.abstract
AB DNA methylation (DNAm) plays an important role in epigenetic regulation of gene expression, orchestrating tissue differentiation and development during all stages of mammalian life. This epigenetic control is especially important in the human brain, with extremely dynamic gene expression during fetal and infant life, and becomes progressively more stable at later periods of development. We characterized the epigenetic state of the developing and aging human frontal cortex in post-mortem tissue from 351 individuals across the lifespan using the Illumina 450k DNA methylation microarray. The largest changes in the methylome occur at birth at varying spatial resolutions – we identify 359,087 differentially methylated loci, which form 23,732 significant differentially methylated regions (DMRs). There were also 298 regions of long-range changes in DNAm, termed “blocks”, associated with birth that strongly overlap previously published colon cancer “blocks”. We then identify 55,439 DMRs associated with development and aging, of which 61.9% significantly associate with nearby gene expression levels. Lastly, we find enrichment of genomic loci of risk for schizophrenia and several other common diseases among these developmental DMRs. These data, integrated with existing genetic and transcriptomic data, create a rich genomic resource across brain development.