- Title:
- Maternal DNA Methylation Regulates Early Trophoblast Development
- Journal:
- Developmental Cell, Volume 36, Issue 2, p152–163, 25 January 2016
- Author(s):
- Branco MR1, King M2, Perez-Garcia V3, Bogutz AB4, Caley M5, Fineberg E2, Lefebvre L4, Cook SJ6, Dean W2, Hemberger M3, Reik W7
- Author(s) affiliation:
- 1Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London E1 2AT, UK. Electronic address: This email address is being protected from spambots. You need JavaScript enabled to view it..
2Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
3Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK.
4Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
5Blizard Institute, Barts and The London School of Medicine and Dentistry, QMUL, London E1 2AT, UK.
6Signalling Programme, Babraham Institute, Cambridge CB22 3AT, UK.
7Epigenetics 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.
- Short description:
- Fertilization marks the start of a cascade of rapid epigenetic changes which, coupled to an intricate network of signaling and transcriptional events, ultimately lead from a totipotent zygote to a myriad of differentiated tissues that comprise the embryo as well as supporting extraembryonic tissues. DNA methylation plays essential roles during this time, mainly by mediating silencing of specific genes and transposable elements. Importantly, while genome-wide DNA methylation erasure occurs after fertilization, key genomic regions are kept methylated, including imprinting control regions (ICRs) and murine intracisternal A-particle (IAP) retrotransposons (Lane et al., 2003, Smith et al., 2012). This epigenetic reprogramming phase is followed by de novo DNA methylation post-implantation, which helps to establish and cement tissue-specific expression programs, thereby driving cell differentiation and organogenesis.
- Link to the journal
Abstract taken from PubMed
- 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.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. - Link to the paper on PubMed
