Epigenetic reprogramming in embryogenesis and the germline

GENE REGULATION, STEM CELLS AND CANCER

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

LAB MANAGER:
Anna Mallol

POSTDOCS:
Pauline Audergon, Shafqat Khan

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

MASTERS/INTERN STUDENTS:
Raffaele Ricci, Nil Ueresin, Marta Puig

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 and test the function of new regulators of this epigenetic reprogramming process. Our goal is to establish how the different steps (e.g. erasure of 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. For this research, Bernhard Payer has been awarded this year the AXA Chair in Risk prediction in age-related diseases by the AXA Research fund.

A successful year for the Payer lab, which has won the second runner-up prize in this year’s ABCAM Image Competition with the image called “Dealing with Gender Balance” (left). The name was coined by PhD-student Jacqueline Severino (left) who also won second poster prize at the CRG PhD-symposium, where PhD-student Moritz Bauer (centre) won first prize for the best talk. Group leader Bernhard Payer (right) holds the leg of jamon (ham), which was given to us by ABCAM together with a basket of delicacies. The image shows a collage of four female mouse blastocyst embryos, which are arranged in the shape of an X, symbolizing the changes happening to the X-chromosome at this stage. Female embryos inactivate one of their two X-chromosomes (yellow spots in the picture), in order to achieve equal X-chromosome expression with males, who have one X and one Y chromosome. In the red cells of the primitive endoderm and the green cells of the trophectoderm female mouse embryos keep the X-chromosome inactive, which they inherited from their father. In the blue-labelled cells of the epiblast, they reactivate the X-chromosome for a short period of time, before inactivating it again in a random fashion. Therefore, this is a critical stage, at which these embryos “deal with their gender balance”.

Fig. 1

A successful year for the Payer lab, which has won the second runner-up prize in this year’s ABCAM Image Competition with the image called “Dealing with Gender Balance” (left). The name was coined by PhD-student Jacqueline Severino (left) who also won second poster prize at the CRG PhD-symposium, where PhD-student Moritz Bauer (centre) won first prize for the best talk. Group leader Bernhard Payer (right) holds the leg of jamon (ham), which was given to us by ABCAM together with a basket of delicacies. The image shows a collage of four female mouse blastocyst embryos, which are arranged in the shape of an X, symbolizing the changes happening to the X-chromosome at this stage. Female embryos inactivate one of their two X-chromosomes (yellow spots in the picture), in order to achieve equal X-chromosome expression with males, who have one X and one Y chromosome. In the red cells of the primitive endoderm and the green cells of the trophectoderm female mouse embryos keep the X-chromosome inactive, which they inherited from their father. In the blue-labelled cells of the epiblast, they reactivate the X-chromosome for a short period of time, before inactivating it again in a random fashion. Therefore, this is a critical stage, at which these embryos “deal with their gender balance”.

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

Selected Publications

Savol AJ, Wang PI, Jeon Y, Colognori D, Yildirim E, Pinter SF, Payer B, Lee JT, and Sadreyev RI.
“Genome-wide identification of autosomal genes with allelic imbalance of chromatin state.”
PLoS ONE 12, e0182568 (2017).

Khan SA, Audergon PNCB and Payer B.
“X-chromosome activity in naïve human pluripotent stem cells – are we there yet?”
Stem Cell Investigation, 4(6):1-9(2017).

Sripathy S, Leko V, Adrianse RL, Loe T, Foss EJ, Dalrymple E, Lao U, Gatbonton-Schwager T, Carter KT, Payer B, Paddison PJ, Grady WM, Lee JT, Bartolomei MS and Bedalov A.
“Screen for reactivation of MeCP2 on the inactive X chromosome identifies the BMP/TGF-β superfamily as a regulator of XIST expression.”
Proc Natl Acad Sci USA, published ahead of print January 31, 2017, doi:10.1073/pnas.1621356114 (2017).

Payer, B.
“Epigenetic Regulation of X-Chromosome Inactivation.”
In: Epigenetics in Human Reproduction and Development, 113-158 (2017).