CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development
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.
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.Attached Files
Published - 1-s2.0-S0092867418315198-main.pdf
Supplemental Material - 1-s2.0-S0092867418315198-mmc1.pdf
Supplemental Material - 1-s2.0-S0092867418315198-mmc2.mp4
Supplemental Material - 1-s2.0-S0092867418315198-mmc3.mp4
Supplemental Material - 1-s2.0-S0092867418315198-mmc4.mp4
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Additional details
- PMCID
- PMC6292842
- Eprint ID
- 94563
- Resolver ID
- CaltechAUTHORS:20190408-111045813
- 098287/Z/12/Z
- Wellcome Trust
- 6699198
- European Research Council (ERC)
- 657995
- Marie Curie Fellowship
- Created
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2019-04-09Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field