Differential regulation of H3S10 phosphorylation, mitosis progression and cell fate by Aurora Kinase B and C in mouse preimplantation embryos.
10.1007/s13238-017-0407-5
- Author:
Wenzhi LI
1
;
Peizhe WANG
1
;
Bingjie ZHANG
2
;
Jing ZHANG
1
;
Jia MING
1
;
Wei XIE
2
;
Jie NA
3
Author Information
1. Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing, 100084, China.
2. Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
3. Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing, 100084, China. jie.na@tsinghua.edu.cn.
- Publication Type:Journal Article
- Keywords:
Aurora kinase;
cell fate;
development;
mitosis;
mouse preimplantation embryo
- MeSH:
Animals;
Aurora Kinase B;
metabolism;
Aurora Kinase C;
metabolism;
Blastocyst;
metabolism;
Gene Expression Regulation, Developmental;
physiology;
Histones;
metabolism;
Mice;
Phosphorylation;
physiology
- From:
Protein & Cell
2017;8(9):662-674
- CountryChina
- Language:English
-
Abstract:
Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect. The kinase domains of AurkB and AurkC were responsible for their different ability to phosphorylate Histone H3 Serine 10 (H3S10P) and regulate metaphase timing. Using an Oct4-photoactivatable GFP fusion protein (Oct4-paGFP) and fluorescence decay after photoactivation assay, we found that AurkB overexpression reduced Oct4 retention in the nucleus. Finally, we show that blastomeres with higher AurkC level elevated pluripotency gene expression, which were inclined to enter the inner cell mass lineage and subsequently contributed to the embryo proper. Collectively, our results are the first demonstration that the activity of mitotic kinases can influence cell fate decisions in mammalian preimplantation embryos and have important implications to assisted reproduction.
