Stella modulates transcriptional and endogenous retrovirus programs during maternal-to-zygotic transition.
The maternal-to-zygotic transition (MZT) marks the period when the embryonic genome is activated and acquires control of development. Maternally inherited factors play a key role in this critical developmental process, which occurs at the 2-cell stage in mice. We investigated the function of the maternally inherited factor Stella (encoded byDppa3) using single-cell/embryo approaches. We show that loss of maternal Stella results in widespread transcriptional mis-regulation and a partial failure of MZT. Strikingly, activation of endogenous retroviruses (ERVs) is significantly impaired in Stella maternal/zygotic knockout embryos, which in turn leads to a failure to upregulate chimeric transcripts. Amongst ERVs, MuERV-L activation is particularly affected by the absence of Stella, and direct in vivo knockdown of MuERV-L impacts the developmental potential of the embryo. We propose that Stella is involved in ensuring activation of ERVs, which themselves play a potentially key role during early development, either directly or through influencing embryonic gene expression.
Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Yun
http://orcid.org/0000-0001-7843-9126
Y
Huang
European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, United Kingdom.|Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea.
Jong Kyoung
JK
Kim
Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Dang Vinh
DV
Do
Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Caroline
C
Lee
Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Christopher A
CA
Penfold
Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Jan J
http://orcid.org/0000-0001-9622-5658
JJ
Zylicz
European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, United Kingdom.|Wellcome Trust Sanger Institute, Cambridge, United Kingdom.|Cancer Research United Kingdom Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
John C
JC
Marioni
Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.|European Molecular Biology Laboratory - Monterotondo, Rome, Italy.
Jamie A
http://orcid.org/0000-0002-6237-3684
JA
Hackett
Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.|Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
M Azim
http://orcid.org/0000-0002-8640-4318
MA
Surani
D000818:Animals; D002454:Cell Differentiation; D002868:Chromosomal Proteins, Non-Histone; D020077:Endogenous Retroviruses / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D012097:Repressor Proteins / Q000378:metabolism*; D015053:Zygote / Q000502:physiology*
D002868:Chromosomal Proteins, Non-Histone; C462180:Dppa3 protein, mouse; D012097:Repressor Proteins
2-cell; MuERV-L/MERVL; Stella; chimeric transcripts; developmental biology; maternal-to-zygotic transition; mouse; stem cells; transposable elements