Re-activation of X-chromosomal Genes Underlies Female Resilience

Gender differences in functionality and vulnerability have been described in many tissues and sexual dimorphism is a phenomenon described for almost any know disease. While hormonal influences and differences in life style provide partial explanations, the fundamental difference in sex chromosome complement is now emerging as a decisive factor and is so far underestimated in gender research.

Genes encoded on the X-chromosome play crucial roles in the development of the nervous and immune systems.  For dosage compensation one of the two X-chromosomes is inactivated in female cells. Several genes have been described to escape X-inactivation in a tissue specific manner. Escape leads to bi-allelic expression and increases gene expression level and diversity in female compared to male cells.

We hypothesize that escape from X-chromosome inactivation is a crucial mechanism underlying female resilience. We will study X-chromosomal gene expression during the development of the nervous and the immune system and link it with tissue functionality. Based on the expertise in genome regulation and stability in our consortium we will look into the molecular mechanisms underlying X-inactivation escape and will explore means to influence the reactivation of select genes.

Finally, we will use a quantitative biomedicine approach to build a model of how the silent X-chromosome changes gears in females and makes them resilient against adverse influences. By elucidating a fundamental mechanism that is substantially involved in the development of organ systems, this project provides the basis for an interdisciplinary approach to understanding female resilience.

Principal Investigators

  • Prof. Dr. Susann Schweiger, University Medical Center Mainz/Leibniz Institute for Resilience Research (contact person, e-mail)
  • Dr. Maria Felicia Basilicata, Institute of Molecular Biology
  • Dr. Joan Barau, Institute of Molecular Biology
  • Prof. Dr. Peter Baumann, Faculty of Biology, JGU/Institute of Molecular Biology
  • Prof. Dr. Benedikt Berninger, University Medical Center Mainz
  • Prof. Dr. Tobias Bopp, University Medical Center Mainz
  • Prof. Dr. Susanne Gerber, University Medical Center Mainz
  • Dr. Claudia Keller-Valsecchi, Institute of Molecular Biology
  • Dr. med. Sebastian Kreiter, TRON
  • Dr. Sabine Muth, University Medical Center Mainz
  • Dr. Hans Christian Probst, University Medical Center Mainz