title: Maternal DNA Methylation Regulates Early Trophoblast Development.
abstract: Critical roles for DNA methylation in embryonic development are well established, but less is known about its roles during trophoblast development, the extraembryonic lineage that gives rise to the placenta. We dissected the role of DNA methylation in trophoblast development by performing mRNA and DNA methylation profiling of Dnmt3a/3b mutants. We find that oocyte-derived methylation plays a major role in regulating trophoblast development but that imprinting of the key placental regulator Ascl2 is only partially responsible for these effects. We have identified several methylation-regulated genes associated with trophoblast differentiation that are involved in cell adhesion and migration, potentially affecting trophoblast invasion. Specifically, trophoblast-specific DNA methylation is linked to the silencing of Scml2, a Polycomb Repressive Complex 1 protein that drives loss of cell adhesion in methylation-deficient trophoblast. Our results reveal that maternal DNA methylation controls multiple differentiation-related and physiological processes in trophoblast via both imprinting-dependent and -independent mechanisms.
authors.affiliation: Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London E1 2AT, UK. Electronic address: m.branco@qmul.ac.uk.
authors.forename: Miguel R
authors.initials: MR
authors.lastname: Branco
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: King
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Vicente
authors.initials: V
authors.lastname: Perez-Garcia
authors.affiliation: Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Bogutz
authors.affiliation: Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London E1 2AT, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Caley
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Fineberg
authors.affiliation: Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Lefebvre
authors.affiliation: Signalling Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Cook
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Dean
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Myriam
authors.initials: M
authors.lastname: Hemberger
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK; The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
authors.forename: Wolf
authors.initials: W
authors.lastname: Reik
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D019175:DNA Methylation; D047108:Embryonic Development / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics; D008822:Mice, Transgenic; D010920:Placenta / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology*
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