TY - JOUR

T1 - Stella modulates transcriptional and endogenous retrovirus programs during maternal-to-zygotic transition

AU - Huang, Yun

AU - Kim, Jong Kyoung

AU - Do, Dang Vinh

AU - Lee, Caroline

AU - Penfold, Christopher A.

AU - Zylicz, Jan J.

AU - Marioni, John C.

AU - Hackett, Jamie A.

AU - Surani, M. Azim

N1 - Funding Information: We thank Richard Butler for his support on the confocal imaging analysis, Charles Bradshaw for bioinformatic support, Todd S Macfarlan and Samuel L Pfaff for the 2C::tdTomato ESCs. We also thank members of the Surani lab for their critical input and helpful discussions on this project. The work was funded by a studentship to YH from the James Baird Fund, University of Cambridge, by the DGIST Start-up Fund of the Ministry of Science, ICT and Future Planning to JKK, by a core grant from EMBL and CRUK to JCM, by a Wellcome Trust Senior Investigator Award to MAS, and by a core grant from the Wellcome Trust and Cancer Research UK to the Gurdon Institute. Publisher Copyright: © Huang et al.

PY - 2017/3/21

Y1 - 2017/3/21

N2 - 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 by Dppa3) using single-cell/embryo approaches. We show that loss of maternal Stella results in widespread transcriptional misregulation 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.

AB - 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 by Dppa3) using single-cell/embryo approaches. We show that loss of maternal Stella results in widespread transcriptional misregulation 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.

UR - http://www.scopus.com/inward/record.url?scp=85018265565&partnerID=8YFLogxK

U2 - 10.7554/eLife.22345

DO - 10.7554/eLife.22345

M3 - Journal article

C2 - 28323615

AN - SCOPUS:85018265565

VL - 6

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e22345

ER -