CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development.
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Authors
Hupalowska, Anna
Jedrusik, Agnieszka
Bedford, Mark T
Glover, David M
Publication Date
2018-12-13Journal Title
Cell
ISSN
0092-8674
Publisher
Elsevier BV
Volume
175
Issue
7
Pages
1902-1916.e13
Language
eng
Type
Article
This Version
VoR
Physical Medium
Print
Metadata
Show full item recordCitation
Hupalowska, A., Jedrusik, A., Zhu, M., Bedford, M. T., Glover, D. M., & Zernicka-Goetz, M. (2018). CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development.. Cell, 175 (7), 1902-1916.e13. https://doi.org/10.1016/j.cell.2018.11.027
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.
Keywords
CARM1, cell fate, development, embryo, heterogeneity, nuclear bodies, p54/nrb, paraspeckles, phase-separation, pre-implantation, Animals, Blastocyst, Cell Cycle Checkpoints, Cell Differentiation, Cell Lineage, Embryonic Development, Mice, Nuclear Matrix-Associated Proteins, Protein-Arginine N-Methyltransferases, RNA, Long Noncoding, RNA-Binding Proteins
Sponsorship
Wellcome Trust (207415/Z/17/Z)
Wellcome Trust (098287/Z/12/Z)
European Commission (657995)
Identifiers
External DOI: https://doi.org/10.1016/j.cell.2018.11.027
This record's URL: https://www.repository.cam.ac.uk/handle/1810/287404
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