TY - JOUR

T1 - G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

AU - Zylicz, Jan J.

AU - Borensztein, Maud

AU - Wong, Frederick C.K.

AU - Huang, Yun

AU - Lee, Caroline

AU - Dietmann, Sabine

AU - Surani, M. Azim

N1 - Funding Information: We are grateful to Alexander Tarakhovsky and Dónal O’Carroll for sharing G9a conditional knockout mice. We thank Dang Vinh Do for critical input into the project and members of the Surani Lab for helpful discussions.The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Wellcome 096738 Jan J Zylicz Maud Borensztein Yun Huang Caroline Lee Sabine Dietmann M Azim Surani. Wellcome RG44593 Jan J Zylicz. H2020 Marie Skłodowska-Curie Actions 706144 Maud Borensztein. Cancer Research UK C6946/A14492 Jan J Zylicz Maud Borensztein Yun Huang Caroline Lee Sabine Dietmann M Azim Surani. James Baird Fund, University of Cambridge Yun Huang. Wellcome 092096 Jan J Zylicz Maud Borensztein Yun Huang Caroline Lee Sabine Dietmann M Azim Surani. Publisher Copyright: © Zylicz et al.

PY - 2018/5/10

Y1 - 2018/5/10

N2 - Early mouse development is regulated and accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2). Previously, we provided insights into its role in post-implantation development (Zylicz et al., 2015). Here we explore the impact of depleting the maternally inherited G9a in oocytes on development shortly after fertilisation. We show that G9a accumulates typically at 4 to 8 cell stage to promote timely repression of a subset of 4 cell stage-specific genes. Loss of maternal inheritance of G9a disrupts the gene regulatory network resulting in developmental delay and destabilisation of inner cell mass lineages by the late blastocyst stage. Our results indicate a vital role of this maternally inherited epigenetic regulator in creating conducive conditions for developmental progression and on cell fate choices.

AB - Early mouse development is regulated and accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2). Previously, we provided insights into its role in post-implantation development (Zylicz et al., 2015). Here we explore the impact of depleting the maternally inherited G9a in oocytes on development shortly after fertilisation. We show that G9a accumulates typically at 4 to 8 cell stage to promote timely repression of a subset of 4 cell stage-specific genes. Loss of maternal inheritance of G9a disrupts the gene regulatory network resulting in developmental delay and destabilisation of inner cell mass lineages by the late blastocyst stage. Our results indicate a vital role of this maternally inherited epigenetic regulator in creating conducive conditions for developmental progression and on cell fate choices.

UR - http://www.scopus.com/inward/record.url?scp=85051932996&partnerID=8YFLogxK

U2 - 10.7554/eLife.33361

DO - 10.7554/eLife.33361

M3 - Journal article

C2 - 29745895

AN - SCOPUS:85051932996

VL - 7

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e33361

ER -