title: Mammalian Brain Development is Accompanied by a Dramatic Increase in Bipolar DNA Methylation.
abstract: DNA methylation is an epigenetic mechanism critical for tissue development and cell specification. Mammalian brains consist of many different types of cells with assumedly distinct DNA methylation profiles, and thus some genomic loci may demonstrate bipolar DNA methylation pattern, i.e. hypermethylated in one cell subset but hypomethylated in others. Currently, how extensive methylation patterns vary among brain cells is unknown and bipolar methylated genomic loci remain largely unexplored. In this study, we implemented a procedure to infer cell-subset specific methylated (CSM) loci from the methylomes of human and mouse frontal cortices at different developmental stages. With the genome-scale hairpin bisulfite sequencing approach, we demonstrated that the majority of CSM loci predicted likely resulted from the methylation differences among brain cells rather than from asymmetric DNA methylation between DNA double strands. Correlated with enhancer-associated histone modifications, putative CSM loci increased dramatically during early stages of brain development and were enriched for GWAS variants associated with neurological disorder-related diseases/traits. Altogether, this study provides a procedure to identify genomic regions showing methylation differences in a mixed cell population and our results suggest that a set of cis-regulatory elements are primed in early postnatal life whose functions may be compromised in human neurological disorders.
authors: Epigenomics and Computational Biology Lab, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, USA.
authors: Ming-An
authors: MA
authors: Sun
authors: Epigenomics and Computational Biology Lab, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, USA.|Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
authors: Zhixiong
authors: Z
authors: Sun
authors: Department of Statistics, Virginia Tech, Blacksburg, VA, USA.
authors: Xiaowei
authors: X
authors: Wu
authors: Department of Pathology, Children's Medical center, Dallas 75235 , USA.|Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75235, USA.
authors: Veena
authors: V
authors: Rajaram
authors: Epigenomics and Computational Biology Lab, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, USA.
authors: David
authors: D
authors: Keimig
authors: Epigenomics and Computational Biology Lab, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, USA.|Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.
authors: Jessica
authors: J
authors: Lim
authors: Department of Statistics, Virginia Tech, Blacksburg, VA, USA.
authors: Hongxiao
authors: H
authors: Zhu
authors: Epigenomics and Computational Biology Lab, Biocomplexity Institute of Virginia Tech, Blacksburg, VA, USA.|Department of Biological Sciences, Virginia Tech, Blacksburg, VA, USA.|School of Neuroscience, Virginia Tech, Blacksburg, VA, USA.|Interdisciplinary Ph.D. Program in Genomics, Bioinformatics, and Computational Biology, Virginia Tech, Blacksburg, VA, USA.|Ph.D. Program in Translational Biology, Medicine, and Health, Virginia Tech, Blacksbury, VA 24061, USA.
authors: Hehuang
authors: H
authors: Xie
mesh_terms: D000293:Adolescent; D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D019175:DNA Methylation; D020869:Gene Expression Profiling / Q000379:methods; D055106:Genome-Wide Association Study / Q000379:methods; D023281:Genomics / Q000379:methods*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008322:Mammals / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D008745:Methylation; D051379:Mice
chemical_list: D006657:Histones