Invited Talk ESA-SRB-ANZBMS 2024 in conjunction with ENSA

FOXL2 interaction with different binding partners regulates the dynamics of ovarian development  (#133)

Roberta Migale 1 , Michelle Neumann 1 , Richard Mitter 2 , Mahmoud-Reza Rafiee 3 , Sophie Wood 4 , Jessica Olsen 4 , Robin Lovell-Badge 1
  1. Laboratory of Stem Cell Biology and Developmental Genetics, The Francis Crick Institute, London, NW1 1AT, UK
  2. Bioinformatics core, The Francis Crick Institute, London NW1 1AT, UK
  3. RNA Networks Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  4. Genetic Modification Service, The Francis Crick Institute, London NW1 1AT, UK

The transcription factor FOXL2 is required in ovarian somatic cells for female fertility. Differential timing of Foxl2 deletion, in embryonic versus adult mouse ovary, leads to distinctive outcomes suggesting different roles across development. Here, we comprehensively investigated FOXL2’s role through a multi-omics approach including chromatin proteomics, transcriptomics, ATAC-Seq and ChIP-Seq. We characterised gene expression dynamics and chromatin accessibility changes, coupled with genome-wide identification of FOXL2 targets and on-chromatin interacting partners in somatic cells across ovarian development. We found that FOXL2 regulates more targets postnatally, through interaction with factors regulating primordial follicle formation and steroidogenesis. One of these interactors was USP7, which plays a role in chromatin remodelling through its histone deubiquitination activity, which can affect gene transcription activation and silencing. We found that USP7 is necessary for the differentiation and proliferation of the somatic cell lineages of the ovary. Deletion of USP7 results in impairment of somatic cell differentiation, germ cell nest breakdown and ovarian development, leading to sterility. Our datasets constitute a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.