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The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.

Publication ,  Journal Article
Muskens, IS; Li, S; Jackson, T; Elliot, N; Hansen, HM; Myint, SS; Pandey, P; Schraw, JM; Roy, R; Anguiano, J; Goudevenou, K; Siegmund, KD ...
Published in: Nat Commun
February 5, 2021

Down syndrome is associated with genome-wide perturbation of gene expression, which may be mediated by epigenetic changes. We perform an epigenome-wide association study on neonatal bloodspots comparing 196 newborns with Down syndrome and 439 newborns without Down syndrome, adjusting for cell-type heterogeneity, which identifies 652 epigenome-wide significant CpGs (P < 7.67 × 10-8) and 1,052 differentially methylated regions. Differential methylation at promoter/enhancer regions correlates with gene expression changes in Down syndrome versus non-Down syndrome fetal liver hematopoietic stem/progenitor cells (P < 0.0001). The top two differentially methylated regions overlap RUNX1 and FLI1, both important regulators of megakaryopoiesis and hematopoietic development, with significant hypermethylation at promoter regions of these two genes. Excluding Down syndrome newborns harboring preleukemic GATA1 mutations (N = 30), identified by targeted sequencing, has minimal impact on the epigenome-wide association study results. Down syndrome has profound, genome-wide effects on DNA methylation in hematopoietic cells in early life, which may contribute to the high frequency of hematological problems, including leukemia, in children with Down syndrome.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 5, 2021

Volume

12

Issue

1

Start / End Page

821

Location

England

Related Subject Headings

  • Proto-Oncogene Protein c-fli-1
  • Promoter Regions, Genetic
  • Male
  • Liver
  • Infant, Newborn
  • Humans
  • Hematopoietic Stem Cells
  • Hematopoiesis
  • Genome-Wide Association Study
  • Genome, Human
 

Citation

APA
Chicago
ICMJE
MLA
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Muskens, I. S., Li, S., Jackson, T., Elliot, N., Hansen, H. M., Myint, S. S., … de Smith, A. J. (2021). The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis. Nat Commun, 12(1), 821. https://doi.org/10.1038/s41467-021-21064-z
Muskens, Ivo S., Shaobo Li, Thomas Jackson, Natalina Elliot, Helen M. Hansen, Swe Swe Myint, Priyatama Pandey, et al. “The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.Nat Commun 12, no. 1 (February 5, 2021): 821. https://doi.org/10.1038/s41467-021-21064-z.
Muskens IS, Li S, Jackson T, Elliot N, Hansen HM, Myint SS, et al. The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis. Nat Commun. 2021 Feb 5;12(1):821.
Muskens, Ivo S., et al. “The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.Nat Commun, vol. 12, no. 1, Feb. 2021, p. 821. Pubmed, doi:10.1038/s41467-021-21064-z.
Muskens IS, Li S, Jackson T, Elliot N, Hansen HM, Myint SS, Pandey P, Schraw JM, Roy R, Anguiano J, Goudevenou K, Siegmund KD, Lupo PJ, de Bruijn MFTR, Walsh KM, Vyas P, Ma X, Roy A, Roberts I, Wiemels JL, de Smith AJ. The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis. Nat Commun. 2021 Feb 5;12(1):821.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 5, 2021

Volume

12

Issue

1

Start / End Page

821

Location

England

Related Subject Headings

  • Proto-Oncogene Protein c-fli-1
  • Promoter Regions, Genetic
  • Male
  • Liver
  • Infant, Newborn
  • Humans
  • Hematopoietic Stem Cells
  • Hematopoiesis
  • Genome-Wide Association Study
  • Genome, Human