DNA-methylation profiling of fetal tissues reveals marked epigenetic differences between chorionic and amniotic samples.
Epigenetic mechanisms including DNA methylation are supposed to play a key role in fetal development. Here we have investigated fetal DNA-methylation levels of 27,578 CpG loci in 47 chorionic villi (CVS) and 16 amniotic cell (AC) samples. Methylation levels differed significantly between karyotypically normal AC and CVS for 2,014 genes. AC showed more extreme DNA-methylation levels of these genes than CVS and the differentially methylated genes are significantly enriched for processes characteristic for the different cell types sampled. Furthermore, we identified 404 genes differentially methylated in CVS with trisomy 21. These genes were significantly enriched for high CG dinucleotid (CpG) content and developmental processes associated with Down syndrome. Our study points to major tissue-specific differences of fetal DNA-methylation and gives rise to the hypothesis that part of the Down syndrome phenotype is epigenetically programmed in the first trimester of pregnancy.
Department of Gynecology & Obstetrics, Christian-Albrechts-University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany.
Christel
C
Eckmann-Scholz
Susanne
S
Bens
Julia
J
Kolarova
Sina
S
Schneppenheim
Almuth
A
Caliebe
Simone
S
Heidemann
Constantin
C
von Kaisenberg
Monika
M
Kautza
Walter
W
Jonat
Reiner
R
Siebert
Ole
O
Ammerpohl
D000650:Amnion / Q000378:metabolism*; D002824:Chorionic Villi / Q000378:metabolism*; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D004314:Down Syndrome / Q000235:genetics; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D005333:Fetus / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D009928:Organ Specificity / Q000235:genetics; D011247:Pregnancy