Projects per year
Abstract
The Zscan4 family of genes, encoding SCAN-domain and zinc finger-containing proteins, has been implicated in the control of early mammalian embryogenesis as well as the regulation of pluripotency and maintenance of genome integrity in mouse embryonic stem cells. However, many features of this enigmatic family of genes are poorly understood. Here we show that undifferentiated mouse embryonic stem cell (ESC) lines simultaneously express multiple members of the Zscan4 gene family, with Zscan4c, Zscan4f and Zscan4-ps2 consistently being the most abundant. Despite this, between only 0.1 and 0.7% of undifferentiated mouse pluripotent stem cells express Zscan4 protein at a given time, consistent with a very restricted pattern of Zscan4 transcripts reported previously. Herein we demonstrate that Zscan4 expression is regulated by the p110α catalytic isoform of phosphoinositide 3-kinases and is induced following exposure to a sub-class of DNA-damage-inducing agents, including Zeocin and Cisplatin. Furthermore, we observe that Zscan4 protein expression peaks during the G2 phase of the cell cycle, suggesting that it may play a critical role at this checkpoint. Studies with GAL4-fusion proteins suggest a role for Zscan4 in transcriptional regulation, further supported by the fact that protein interaction analyses demonstrate that Zscan4 interacts with both LSD1 and CtBP2 in ESC nuclei. This study advances and extends our understanding of Zscan4 expression, regulation and mechanism of action. Based on our data we propose that Zscan4 may regulate gene transcription in mouse ES cells through interaction with LSD1 and CtBP2.
Original language | English |
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Journal | PLoS ONE |
Volume | 9 |
Issue number | 3 |
DOIs | |
Publication status | Published - 3 Mar 2014 |
Fingerprint
Dive into the research topics of 'Zscan4 is regulated by PI3-kinase and DNA-damaging agents and directly interacts with the transcriptional repressors LSD1 and CtBP2 in mouse embryonic stem cells'. Together they form a unique fingerprint.Projects
- 1 Finished
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Regulation of Embryonic Stem Cell Self Renewal by the Zscan4 Family of Zinc Finger Proteins
Welham, M. J. (PI)
1/05/09 → 30/04/12
Project: Research council
Profiles
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Julian Chaudhuri
- Vice Chancellor's Office - Pro-Vice-Chancellor (Education & Global)
- Centre for Bioengineering & Biomedical Technologies (CBio)
Person: Research & Teaching, Affiliate staff
Equipment
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Epi-fluorescent microscope Leica Dmi8 in hypoxic cabinet
Material and Chemical Characterisation (MC2)Facility/equipment: Equipment
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Flow Cytometer - BD FACSCanto II
Material and Chemical Characterisation (MC2)Facility/equipment: Equipment
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MC2-Bioimaging and cell analysis
Material and Chemical Characterisation (MC2)Facility/equipment: Technology type