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.