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CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development

Hupalowska, Anna and Jedrusik, Agnieszka and Zhu, Meng and Bedford, Mark T. and Glover, David M. and Zernicka-Goetz, Magdalena (2018) CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development. Cell, 175 (7). 1902-1916.e13. ISSN 0092-8674. PMCID PMC6292842. http://resolver.caltech.edu/CaltechAUTHORS:20190408-111045813

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Abstract

Nuclear architecture has never been carefully examined during early mammalian development at the stages leading to establishment of the embryonic and extra-embryonic lineages. Heterogeneous activity of the methyltransferase CARM1 during these stages results in differential methylation of histone H3R26 to modulate establishment of these two lineages. Here we show that CARM1 accumulates in nuclear granules at the 2- to 4-cell stage transition in the mouse embryo, with the majority corresponding to paraspeckles. The paraspeckle component Neat1 and its partner p54nrb are required for CARM1’s association with paraspeckles and for H3R26 methylation. Conversely, CARM1 also influences paraspeckle organization. Depletion of Neat1 or p54nrb results in arrest at the 16- to 32-cell stage, with elevated expression of transcription factor Cdx2, promoting differentiation into the extra-embryonic lineage. This developmental arrest occurs at an earlier stage than following CARM1 depletion, indicating that paraspeckles act upstream of CARM1 but also have additional earlier roles in fate choice.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.cell.2018.11.027DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292842/PubMed CentralArticle
ORCID:
AuthorORCID
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2018 The Authors. Published by Elsevier Under a Creative Commons license (Attribution 4.0 International (CC BY 4.0)) Received 24 March 2018, Revised 29 July 2018, Accepted 16 November 2018, Available online 13 December 2018. We are grateful to colleagues from the M.Z.-G. lab for discussions and feedback. We are grateful to Marta Shahbazi for critically reading the manuscript. This work was supported by the Wellcome Trust (grant 098287/Z/12/Z) and European Union ERC (grant 6699198 to M.Z.-G.). A.H. was supported by a Marie Curie Individual Fellowship (MC-IF, Horizon 2020, grant 657995). Author Contributions: Conceptualization, A.H.; Investigation, A.H., A.J., and M.Z.; Resources and Construction of Carm1 Transgenic Mice, M.T.B.; Writing – Original Draft, A.H., D.M.G., and M.Z.-G.; Writing – Review & Editing, A.H., D.M.G., and M.Z.-G.; Visualization, A.H.; Funding Acquisition, A.H. and M.Z.-G.; Supervision, D.M.G. and M.Z.-G. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
Wellcome Trust098287/Z/12/Z
European Research Council (ERC)6699198
Marie Curie Fellowship657995
Subject Keywords:paraspeckles; nuclear bodies; phase-separation; CARM1; p54/nrb; pre-implantation; embryo; development; heterogeneity; cell fate
PubMed Central ID:PMC6292842
Record Number:CaltechAUTHORS:20190408-111045813
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20190408-111045813
Official Citation:Anna Hupalowska, Agnieszka Jedrusik, Meng Zhu, Mark T. Bedford, David M. Glover, Magdalena Zernicka-Goetz, CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development, Cell, Volume 175, Issue 7, 2018, Pages 1902-1916.e13, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2018.11.027. (http://www.sciencedirect.com/science/article/pii/S0092867418315198)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94563
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Apr 2019 14:41
Last Modified:09 Apr 2019 14:41

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