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Epigenomics. 2017 Feb;9(2):189-207. doi: 10.2217/epi-2016-0138. Epub 2016 Dec 2.

Trans-acting epigenetic effects of chromosomal aneuploidies: lessons from Down syndrome and mouse models.

Do C1, Xing Z2, Yu YE2, Tycko B1,3,4,5.

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Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA.
The Children's Guild Foundation Down Syndrome Research Program, Genetics Program & Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Taub Institute for Research on Alzheimer's disease & the Aging Brain, Columbia University, New York, NY 10032, USA.
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.

Erratum in


An important line of postgenomic research seeks to understand how genetic factors can influence epigenetic patterning. Here we review epigenetic effects of chromosomal aneuploidies, focusing on findings in Down syndrome (DS, trisomy 21). Recent work in human DS and mouse models has shown that the extra chromosome 21 acts in trans to produce epigenetic changes, including differential CpG methylation (DS-DM), in specific sets of downstream target genes, mostly on other chromosomes. Mechanistic hypotheses emerging from these data include roles of chromosome 21-linked methylation pathway genes (DNMT3L and others) and transcription factor genes (RUNX1, OLIG2, GABPA, ERG and ETS2) in shaping the patterns of DS-DM. The findings may have broader implications for trans-acting epigenetic effects of chromosomal and subchromosomal aneuploidies in other human developmental and neuropsychiatric disorders, and in cancers.


CTCF; DNA methylation; Down syndrome; aneuploidy; cancer; chromatin; developmental disorders; methyltransferases; mouse models; transcription factors

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