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Latos PA, Helliwell C, Mosaku O, et al. NuRD-dependent DNA methylation prevents ES cells from accessing a trophectoderm fate. Biol Open. 2012;1(4):341-52doi: 10.1242/bio.2012513.
Latos, P. A., Helliwell, C., Mosaku, O., Dudzinska, D. A., Stubbs, B., Berdasco, M., Esteller, M., & Hendrich, B. (2012). NuRD-dependent DNA methylation prevents ES cells from accessing a trophectoderm fate. Biology open, 1(4), 341-52. https://doi.org/10.1242/bio.2012513
Latos, Paulina A, et al. "NuRD-dependent DNA methylation prevents ES cells from accessing a trophectoderm fate." Biology open vol. 1,4 (2012): 341-52. doi: https://doi.org/10.1242/bio.2012513
Latos PA, Helliwell C, Mosaku O, Dudzinska DA, Stubbs B, Berdasco M, Esteller M, Hendrich B. NuRD-dependent DNA methylation prevents ES cells from accessing a trophectoderm fate. Biol Open. 2012 Apr 15;1(4):341-52. doi: 10.1242/bio.2012513. Epub 2012 Feb 07. PMID: 23213424; PMCID: PMC3509455.
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Biol Open. 2012 Apr 15;1(4):341-52. doi: 10.1242/bio.2012513. Epub 2012 Feb 07.

NuRD-dependent DNA methylation prevents ES cells from accessing a trophectoderm fate.

Biology open

Paulina A Latos, Christine Helliwell, Olukunbi Mosaku, Dominika A Dudzinska, Bryony Stubbs, Maria Berdasco, Manel Esteller, Brian Hendrich

Affiliations

  1. Wellcome Trust Centre for Stem Cell Research, MRC Centre for Stem Cell Biology and Regenerative Medicine, University of Cambridge , Tennis Court Road, Cambridge, CB2 1QR , UK ; Babraham Institute, Babraham Research Campus , Cambridge, CB22 3AT , UK.

PMID: 23213424 PMCID: PMC3509455 DOI: 10.1242/bio.2012513

Abstract

Embryonic Stem (ES) cells are able to give rise to the three germ layers of the embryo but are prevented from contributing to the trophoblast. The molecular nature of this barrier between embryonic and trophectodermal cell fates is not clear, but is known to involve DNA methylation. Here we demonstrate that the Nucleosome Remodeling and Deacetylation (NuRD) co-repressor complex maintains the developmental barrier between embryonic and trophectodermal cell fates by maintaining transcriptional silencing of trophectoderm determinant genes in ES cells. We further show that NuRD activity facilitates DNA methylation of several of its target promoters, where it acts non-redundantly with DNA methylation to enforce transcriptional silencing. NuRD-deficient ES cells fail to completely silence expression of the trophectoderm determinant genes Elf5 and Eomes, but this alone is not sufficient to induce transdifferentiation towards the trophectoderm fate. Rather this leaves ES cells capable of activating expression of trophectoderm-specific genes in response to appropriate extracellular signals, enabling them to commit to a trophectodermal cell fate. Our findings clarify the molecular nature of the developmental barrier between the embryonic and trophoblast cell fates, and establish a role for NuRD activity in specifying sites for de novo DNA methylation.

Keywords: Chromatin; DNA methylation; NuRD; Stem cells; Trophectoderm

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