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Epigenetic Modification Affecting Expression of Cell Polarity and Cell Fate Genes to Regulate Lineage Specification in the Early Mouse Embryo

Parfitt, David-Emlyn and Zernicka-Goetz, Magdalena (2010) Epigenetic Modification Affecting Expression of Cell Polarity and Cell Fate Genes to Regulate Lineage Specification in the Early Mouse Embryo. Molecular Biology of the Cell, 21 (15). pp. 2649-2660. ISSN 1059-1524. PMCID PMC2912351. https://resolver.caltech.edu/CaltechAUTHORS:20190417-163114865

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Abstract

Formation of inner and outer cells of the mouse embryo distinguishes pluripotent inner cell mass (ICM) from differentiating trophectoderm (TE). Carm1, which methylates histone H3R17 and R26, directs cells to ICM rather that TE. To understand the mechanism by which this epigenetic modification directs cell fate, we generated embryos with in vivo–labeled cells of different Carm1 levels, using time-lapse imaging to reveal dynamics of their behavior, and related this to cell polarization. This shows that Carm1 affects cell fate by promoting asymmetric divisions, that direct one daughter cell inside, and cell engulfment, where neighboring cells with lower Carm1 levels compete for outside positions. This is associated with changes to the expression pattern and spatial distribution of cell polarity proteins: Cells with higher Carm1 levels show reduced expression and apical localization of Par3 and a dramatic increase in expression of PKCII, antagonist of the apical protein aPKC. Expression and basolateral localization of the mouse Par1 homologue, EMK1, increases concomitantly. Increased Carm1 also reduces Cdx2 expression, a transcription factor key for TE differentiation. These results demonstrate how the extent of a specific epigenetic modification could affect expression of cell polarity and fate-determining genes to ensure lineage allocation in the mouse embryo.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1091/mbc.e10-01-0053DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912351/PubMed CentralArticle
https://www.molbiolcell.org/doi/suppl/10.1091/mbc.e10-01-0053PublisherSupporting Information
ORCID:
AuthorORCID
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2010 by The American Society for Cell Biology. Authors grant to the general public, effective two months after publication of (i.e.,. the appearance of the edited manuscript in an online issue of MBoC), the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0). Submitted: 21 January 2010. Revised: 21 April 2010. Accepted: 3 June 2010. We are grateful to M.Z.-G. lab members for support and discussions and to Kat Hadjantonakis (Sloan-Kettering, New York, NY) and Ginny Papaioannou (Columbia University, New York, NY) for the reporter transgenic line. This work was supported by the Wellcome Trust Senior Research Fellowship to M.Z.-G. and MCR Studentship to D.-E.P.
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Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
Issue or Number:15
PubMed Central ID:PMC2912351
Record Number:CaltechAUTHORS:20190417-163114865
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190417-163114865
Official Citation:Epigenetic Modification Affecting Expression of Cell Polarity and Cell Fate Genes to Regulate Lineage Specification in the Early Mouse Embryo David-Emlyn Parfitt and Magdalena Zernicka-Goetz Molecular Biology of the Cell 2010 21:15, 2649-2660
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94772
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:18 Apr 2019 20:40
Last Modified:03 Oct 2019 21:07

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