GROUP LEADER: Bernhard Payer (AXA Professor of Risk prediction in age-related diseases since October 2017)

LAB MANAGER: Anna Mallol

POSTDOCTORAL FELLOWS: Pauline Audergon, Shafqat Khan

PhD STUDENTS: Moritz Bauer, Mercedes Barrero, Serena Generoso, Jacqueline Severino, Antonio Tarruell

MASTERS/INTERN STUDENTS: Marta Puig, Annagiulia Ciocia

SUMMARY

Epigenetic mechanisms control interpretation of the genome, which is identical between cell types. The inactivation of one of the two X-chromosomes in female mammals is a prominent example of such epigenetic regulation, in which gene expression from an entire X-chromosome is suppressed to avoid gene dosage imbalance with males, which only have a single X.

In our group, we study the mechanisms of X-chromosome reactivation, which reverses X-inactivation. We make use of in vivo and in vitro approaches to identify new regulators of this epigenetic reprogramming process. Our goal is to establish how the different steps (e.g. changes in 3D-chromatin structure, epigenetic marks, X-linked gene reactivation) are achieved and how they are linked to their biological context within pluripotent cells and in the germ line.

Furthermore, we are studying in collaboration with the fertility Clinic Eugin, what effects age has on epigenetic mechanisms affecting the quality of human oocytes. With this research, we want to apply our expertise in germ cell development and epigenetics to address clinical outcomes of reproductive aging.

(A) Oocyte development relies on fine-tuned signalling interactions with gonadal somatic cells. This can be appreciated by this 3D-printed model (1000x larger than original) of a growing mouse oocyte (large cell with pink nucleus) surrounded by somatic cumulus cells (small cells at the top). (B) X-chromosome inactivation is a classic example of epigenetics, where the same DNA-sequence (active Xa versus inactive Xi) can show very different gene expression states and 3D-structure depending on epigenetic regulation. (C) In collaboration with members of the ERC 4D-Genome synergy unit (Guillaume Filion, Enrique Vidal), we study 3D-structural changes, which occur depending on different states of the X-chromosome (Hi-C image with 3D-interactions along the X).

Fig. 1

(A) Oocyte development relies on fine-tuned signalling interactions with gonadal somatic cells. This can be appreciated by this 3D-printed model (1000x larger than original) of a growing mouse oocyte (large cell with pink nucleus) surrounded by somatic cumulus cells (small cells at the top). (B) X-chromosome inactivation is a classic example of epigenetics, where the same DNA-sequence (active Xa versus inactive Xi) can show very different gene expression states and 3D-structure depending on epigenetic regulation. (C) In collaboration with members of the ERC 4D-Genome synergy unit (Guillaume Filion, Enrique Vidal), we study 3D-structural changes, which occur depending on different states of the X-chromosome (Hi-C image with 3D-interactions along the X).

RESEARCH PROJECTS

  • X-chromosome reactivation during stem cell reprogramming
  • Epigenetic reprogramming in the germ cell lineage in vivo and in vitro
  • Mechanism of epigenetic inheritance between generations
  • Understanding the epigenetic effects of aging on human oocytes