CARM1 and Paraspeckles Regulate Pre-implantation Mouse Embryo Development.
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Authors
Hupalowska, Anna
Jedrusik, Agnieszka
Bedford, Mark T
Publication Date
2018-12Journal Title
Cell
ISSN
0092-8674
Publisher
Elsevier
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., & 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 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, the majority corresponding to paraspeckles. The paraspeckle components, 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
Blastocyst, Animals, Mice, RNA-Binding Proteins, Nuclear Matrix-Associated Proteins, Cell Differentiation, Cell Lineage, Embryonic Development, Protein-Arginine N-Methyltransferases, Cell Cycle Checkpoints, RNA, Long Noncoding
Sponsorship
European Commission (657995)
Wellcome Trust (098287/Z/12/Z)
Wellcome Trust (207415/Z/17/Z)
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