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Mammalian Genome

, Volume 22, Issue 11–12, pp 722–735 | Cite as

Hypomethylation of functional retrotransposon-derived genes in the human placenta

  • Erin C. Macaulay
  • Robert J. Weeks
  • Simon Andrews
  • Ian M. MorisonEmail author
Article

Abstract

DNA hypomethylation is assumed to be a feature of the mammalian placenta; however, its role in regulating placental gene expression is not well defined. In this study, MeDIP and Sequenom MassARRAY were used to identify hypomethylated gene promoters in the human placenta. Among the genes identified, the hypomethylation of an alternative promoter for KCNH5 was found to be restricted to the placenta and chorion. Complete methylation of this promoter correlates with a silenced KCNH5 transcript in embryonic tissues, including the amnion. Unusually, this hypomethylated promoter and the alternative first exon are derived from a SINE (AluY) retrotransposon. Examination of additional retrotransposon-derived gene promoters in the placenta confirmed that retrotransposon hypomethylation permits the placenta-specific expression of these genes. Furthermore, the lineage-specific methylation displayed by KCNH5, INSL4, and ERVWE1 revealed that dichotomous methylation establishes differential retrotransposon silencing between the extra-embryonic and embryonic lineages. The hypomethylation of the retrotransposons that regulate these genes, each of which arose during recent primate evolution, is consistent with these genes having functional roles that are unique to the invasive haemochorial placentas of humans and recent primates.

Keywords

Promoter Methylation Primitive Endoderm Aviva System Biology Placental Gene Expression Adult Somatic Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank the women who donated their pregnancy tissues to this study. We acknowledge funding from the University of Otago and the National Research Centre for Growth and Development.

Supplementary material

335_2011_9355_MOESM1_ESM.pdf (121 kb)
Supplementary material 1 (PDF 121 kb)
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Supplementary material 2 (PDF 164 kb)
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Supplementary material 3 (PDF 96 kb)
335_2011_9355_MOESM4_ESM.pdf (119 kb)
Supplementary material 4 (PDF 120 kb)
335_2011_9355_MOESM5_ESM.doc (341 kb)
Supplementary material 5 (DOC 341 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Erin C. Macaulay
    • 1
  • Robert J. Weeks
    • 2
  • Simon Andrews
    • 3
  • Ian M. Morison
    • 1
    Email author
  1. 1.Department of Pathology, Dunedin School of Medicine and National Research Centre for Growth and DevelopmentUniversity of OtagoDunedinNew Zealand
  2. 2.Department of Pathology, Dunedin School of MedicineUniversity of OtagoDunedinNew Zealand
  3. 3.Bioinformatics GroupThe Babraham InstituteCambridgeUK

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