title: Global DNA hypermethylation in down syndrome placenta.
abstract: Down syndrome (DS), commonly caused by an extra copy of chromosome 21 (chr21), occurs in approximately one out of 700 live births. Precisely how an extra chr21 causes over 80 clinically defined phenotypes is not yet clear. Reduced representation bisulfite sequencing (RRBS) analysis at single base resolution revealed DNA hypermethylation in all autosomes in DS samples. We hypothesize that such global hypermethylation may be mediated by down-regulation of TET family genes involved in DNA demethylation, and down-regulation of REST/NRSF involved in transcriptional and epigenetic regulation. Genes located on chr21 were up-regulated by an average of 53% in DS compared to normal villi, while genes with promoter hypermethylation were modestly down-regulated. DNA methylation perturbation was conserved in DS placenta villi and in adult DS peripheral blood leukocytes, and enriched for genes known to be causally associated with DS phenotypes. Our data suggest that global epigenetic changes may occur early in development and contribute to DS phenotypes.
authors.affiliation: Growth, Development and Metabolism Program, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Jin
authors.forename: Yew Kok
authors.initials: YK
authors.lastname: Lee
authors.forename: Yen Ching
authors.initials: YC
authors.lastname: Lim
authors.forename: Zejun
authors.initials: Z
authors.lastname: Zheng
authors.forename: Xueqin Michelle
authors.initials: XM
authors.lastname: Lin
authors.forename: Desmond P Y
authors.initials: DP
authors.lastname: Ng
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Holbrook
authors.forename: Hai Yang
authors.initials: HY
authors.lastname: Law
authors.forename: Kenneth Y C
authors.initials: KY
authors.lastname: Kwek
authors.forename: George S H
authors.initials: GS
authors.lastname: Yeo
authors.forename: Chunming
authors.initials: C
authors.lastname: Ding
mesh_terms: D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D000099229:RE1-Silencing Transcription Factor
chemical_list: D004268:DNA-Binding Proteins; D049308:Dioxygenases; D006899:Mixed Function Oxygenases; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C462539:TET1 protein, human; C541081:TET2 protein, human