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Abstract
Remodelling the methylome is a hallmark of mammalian development and cell differentiation. However, current knowledge of DNA methylation dynamics in human tissue specification and organ development largely stems from the extrapolation of studies in vitro and animal models. Here, we report on the DNA methylation landscape using the 450k array of four human tissues (amnion, muscle, adrenal and pancreas) during the first and second trimester of gestation (9,18 and 22 weeks). We show that a tissue-specific signature, constituted by tissue-specific hypomethylated CpG sites, was already present at 9 weeks of gestation (W9). Furthermore, we report large-scale remodelling of DNA methylation from W9 to W22. Gain of DNA methylation preferentially occurred near genes involved in general developmental processes, whereas loss of DNA methylation mapped to genes with tissue-specific functions. Dynamic DNA methylation was associated with enhancers, but not promoters. Comparison of our data with external fetal adrenal, brain and liver revealed striking similarities in the trajectory of DNA methylation during fetal development. The analysis of gene expression data indicated that dynamic DNA methylation was associated with the progressive repression of developmental programs and the activation of genes involved in tissue-specific processes. The DNA methylation landscape of human fetal development provides insight into regulatory elements that guide tissue specification and lead to organ functionality.
Keywords
HUMAN GENOME, EPIGENETIC EPIDEMIOLOGY, EMBRYONIC STEM-CELLS, PROGENITOR CELLS, DYNAMIC CHANGES, BETA-CELL, DIFFERENTIATION, TISSUE, DEMETHYLATION, TRANSCRIPTION FACTORS

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MLA
Slieker, Roderick C., et al. “DNA Methylation Landscapes of Human Fetal Development.” PLOS GENETICS, vol. 11, no. 10, 2015, doi:10.1371/journal.pgen.1005583.
APA
Slieker, R. C., Roost, M. S., van Iperen, L., Suchiman, H. E. D., Tobi, E. W., Carlotti, F., … Chuva de Sousa Lopes, S. M. (2015). DNA methylation landscapes of human fetal development. PLOS GENETICS, 11(10). https://doi.org/10.1371/journal.pgen.1005583
Chicago author-date
Slieker, Roderick C, Matthias S Roost, Liesbeth van Iperen, H Eka D Suchiman, Elmar W Tobi, Françoise Carlotti, Eelco JP de Koning, P Eline Slagboom, Bastiaan T Heijmans, and Susana Marina Chuva de Sousa Lopes. 2015. “DNA Methylation Landscapes of Human Fetal Development.” PLOS GENETICS 11 (10). https://doi.org/10.1371/journal.pgen.1005583.
Chicago author-date (all authors)
Slieker, Roderick C, Matthias S Roost, Liesbeth van Iperen, H Eka D Suchiman, Elmar W Tobi, Françoise Carlotti, Eelco JP de Koning, P Eline Slagboom, Bastiaan T Heijmans, and Susana Marina Chuva de Sousa Lopes. 2015. “DNA Methylation Landscapes of Human Fetal Development.” PLOS GENETICS 11 (10). doi:10.1371/journal.pgen.1005583.
Vancouver
1.
Slieker RC, Roost MS, van Iperen L, Suchiman HED, Tobi EW, Carlotti F, et al. DNA methylation landscapes of human fetal development. PLOS GENETICS. 2015;11(10).
IEEE
[1]
R. C. Slieker et al., “DNA methylation landscapes of human fetal development,” PLOS GENETICS, vol. 11, no. 10, 2015.
@article{7016518,
  abstract     = {{Remodelling the methylome is a hallmark of mammalian development and cell differentiation. However, current knowledge of DNA methylation dynamics in human tissue specification and organ development largely stems from the extrapolation of studies in vitro and animal models. Here, we report on the DNA methylation landscape using the 450k array of four human tissues (amnion, muscle, adrenal and pancreas) during the first and second trimester of gestation (9,18 and 22 weeks). We show that a tissue-specific signature, constituted by tissue-specific hypomethylated CpG sites, was already present at 9 weeks of gestation (W9). Furthermore, we report large-scale remodelling of DNA methylation from W9 to W22. Gain of DNA methylation preferentially occurred near genes involved in general developmental processes, whereas loss of DNA methylation mapped to genes with tissue-specific functions. Dynamic DNA methylation was associated with enhancers, but not promoters. Comparison of our data with external fetal adrenal, brain and liver revealed striking similarities in the trajectory of DNA methylation during fetal development. The analysis of gene expression data indicated that dynamic DNA methylation was associated with the progressive repression of developmental programs and the activation of genes involved in tissue-specific processes. The DNA methylation landscape of human fetal development provides insight into regulatory elements that guide tissue specification and lead to organ functionality.}},
  articleno    = {{e1005583}},
  author       = {{Slieker, Roderick C and Roost, Matthias S and van Iperen, Liesbeth and Suchiman, H Eka D and Tobi, Elmar W and Carlotti, Françoise and de Koning, Eelco JP and Slagboom, P Eline and Heijmans, Bastiaan T and Chuva de Sousa Lopes, Susana Marina}},
  issn         = {{1553-7404}},
  journal      = {{PLOS GENETICS}},
  keywords     = {{HUMAN GENOME,EPIGENETIC EPIDEMIOLOGY,EMBRYONIC STEM-CELLS,PROGENITOR CELLS,DYNAMIC CHANGES,BETA-CELL,DIFFERENTIATION,TISSUE,DEMETHYLATION,TRANSCRIPTION FACTORS}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{19}},
  title        = {{DNA methylation landscapes of human fetal development}},
  url          = {{http://doi.org/10.1371/journal.pgen.1005583}},
  volume       = {{11}},
  year         = {{2015}},
}

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