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DNA Methylation Divergence and Tissue Specialization in the Developing Mouse Placenta

Accepted version
Peer-reviewed

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Type

Article

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Authors

Decato, BE 
Lopez-Tello, J 
Sferruzzi-Perri, AN 
Smith, AD 
Dean, MD 

Abstract

The placental epigenome plays a vital role in regulating mammalian growth and development. Aberrations in placental DNA methylation are linked to several disease states, including intrauterine growth restriction and preeclampsia. Studying the evolution and development of the placental epigenome is critical to understanding the origin and progression of such diseases. Although high-resolution studies have found substantial variation between placental methylomes of different species, the nature of methylome variation has yet to be characterized within any individual species. We conducted a study of placental DNA methylation at high resolution in multiple strains and closely related species of house mice (Mus musculus musculus, Mus m. domesticus, and M. spretus), across developmental timepoints (embryonic days 15-18), and between two distinct layers (labyrinthine transport and junctional endocrine). We observed substantial genome-wide methylation heterogeneity in mouse placenta compared with other differentiated tissues. Species-specific methylation profiles were concentrated in retrotransposon subfamilies, specifically RLTR10 and RLTR20 subfamilies. Regulatory regions such as gene promoters and CpG islands displayed cross-species conservation, but showed strong differences between layers and developmental timepoints. Partially methylated domains exist in the mouse placenta and widen during development. Taken together, our results characterize the mouse placental methylome as a highly heterogeneous and deregulated landscape globally, intermixed with actively regulated promoter and retrotransposon sequences.

Description

Keywords

DNA methylation, epigenome, junctional zone, labyrinthine zone, placenta

Journal Title

Molecular Biology and Evolution

Conference Name

Journal ISSN

0737-4038
1537-1719

Volume Title

34

Publisher

Oxford University Press
Sponsorship
Funding was provided by an EU COST ACTION grant and Erasmus Traineeship (J.L.T.), a Royal Society Dorothy Hodgkin Fellowship (A.N.S.P.), and National Insitutes of Health grants GM098536 (M.D.D.) and HG005238 (A.D.S.).