Characterization of non-canonical Polycomb Repressive Complex 1 subunits during early mouse embryogenesis

ABSTRACT

An intense period of chromatin remodeling takes place after fertilization in mammals, which is thought necessary for epigenetic reprogramming to start a new developmental program. While much attention has been given to the role of Polycomb Repressive Complex 2 (PRC2) and to canonical PRC1 complexes during this process, little is known as to whether there is any contribution of non-canonical PRC1 in shaping the chromatin landscape after fertilization. Here, we first describe in detail the temporal dynamics and abundance of H2A ubiquitylation (H2AK119ub), a histone modification catalyzed by PRC1, during pre-implantation mouse development. In addition, we have analyzed the presence of the 2 characteristic subunits of non-canonical PRC1 complexes, RYBP and its homolog YAF-2. Our results indicate that H2AK119ub is inherited from the sperm, rapidly removed from the paternal chromatin after fertilization, but detected again prior to the first mitosis, suggesting that PRC1 activity occurs as early as the zygotic stage. RYBP and YAF-2, together with the non-canonical subunit L3MBTL2, are all present during pre-implantation development but show different temporal dynamics. While RYBP is absent in the zygote, it is strongly induced from the 4-cell stage onwards. YAF-2 is inherited maternally and localizes to the pericentromeric regions in the zygote, is strongly induced between the 2- and 4-cell stages but then remains weak to undetectable subsequently. All together, our data suggest that non-canonical PRC1 is active during pre-implantation development and should be regarded as an additional component during epigenetic reprogramming and in the establishment of cellular plasticity of the early embryo.

KEYWORDS:

• Epigenetic reprogramming
• histone modification
• mouse embryo
• PRC1

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We are grateful to Jin Zhang, Patrick Trojer and Danny Reinberg for providing the L3MBTL1 and L3MBTL2 antibodies and to Celine Ziegler-Birling for support with mouse handling and embryo collection. M.E.T.-P. acknowledges funding from EpiGeneSys NoE, ERC-Stg ‘NuclearPotency’, EMBO Young Investigator Program and the Schlumberger Foundation for Research and Education. A.E is a recipient of a doctoral fellowship from the Ministère de l'Enseignement Supérieur et de la Recherche and from the Fondation pour la Recherche Médicale (FDT20150532012).