"Investigating the role of Polycomb in epigenetic regulation and inheritance during mouse germline formation and embryogenesis: study of a new member of the PRC2 complex, EZHIP (Ezh2 Inhibitory Protein) using transgenic model (2022-11-MARGUERON_ANCELIN)" project details

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2022-11-MARGUERON_ANCELIN

Intergenerational epigenetic inheritance; Histone modifications; Polycomb; Mouse embryogenesis; Germline

Investigating the role of Polycomb in epigenetic regulation and inheritance during mouse germline formation and embryogenesis: study of a new member of the PRC2 complex, EZHIP (Ezh2 Inhibitory Protein) using transgenic model

Director(s) and team

Raphaƫl Margueron & Katia Ancelin

Maintenance of Transcriptional Repression by Polycomb Proteins

Abstract

During ontogeny, chromatin modifiers contribute to the orchestration of spatiotemporal gene expression programs that underlie early development and organogenesis. The Polycomb repressive complex 2 (PRC2) is one of such central epigenetic remodelers. It is key for transmitting correct chromatin information from parent to offspring during the formation of the mouse germline. PRC2 methylates lysine 27 on histone H3 (H3K27me2/3), a crucial step for the formation of closed chromatin structure refractory to transcription. PRC2 cofactors modulates its enzymatic activity, influencing the H3K27me3 pattern. Among them, we recently characterized EZHIP as a negative regulator of PRC2 in gametes. Although Ezhip KO animals are viable, mouse females display a reduce fertility phenotype.   We are currently investigating phenotypic and molecular changes upon maternal loss of EZHIP in oocyte, we have already gathered important results concerning its role in maintenance of gene imprinting in the progeny. Besides, preliminary evidences indicate that upon loss of maternal and paternal EZHIP, the progeny displays a variety of subtle phenotypes. Further investigation is needed to understand how PRC2-dependent transcriptional changes affect early post-natal life and adulthood.   This project will aim at deciphering the role of paternal EZHIP in the germline and upon its transmission at different stage of mouse life, using low input CUT&RUN and RNAseq technologies to assess chromatin and transcriptional changes.

Requirements to apply for the PhD thesis project

Applicants should have a strong interest for early development and epigenetic. They should have good communication skills, be self-motivated, adaptable and able to work in an innovative and challenging scientific environment. The project implies mouse genetics and bioinformatic.