Meet the jury lecture: DNA Modifications and (hetero)chromatin compartmentalization by prof. Cristina Cardoso

You are kindly invited to the Meet the jury lecture on ‘DNA Modifications and (hetero)chromatin compartmentalization’ by Prof. M. Cristina Cardoso, Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, Germany

Date: 16/01/25, 11h-12h
Location: BMW 3, ON2, Campus Gasthuisberg

About the lecture

From yeast to man, the genome is non-homogenously packed within the cell nucleus. This spatial compartmentalization is highly dynamic during development and in disease and regulates genome activity.  Heterochromatin is the highly compacted form of chromatin and hallmarked by high DNA methylation in mammals. MeCP2 and other members of the methylcytosine binding domain protein family are DNA methylation readers and have also been reported as heterochromatin organizers MECP2 gene mutations were found in circa 90% of patients with a human neurological disorder called Rett syndrome and affect chromatin organization. Binding of MeCP2 protein to heterochromatin protects methylcytosine from further oxidation by the TET (Ten-Eleven Translocation) dioxygenase enzymes, thus, lowering transcriptional noise. By combining liquid-liquid phase separation (LLPS) analysis and single-molecule tracking with quantification of local MeCP2 concentrations in vitro and in vivo, we explored the mechanism of MeCP2-driven heterochromatin compartmentalization and dynamics. We show that MeCP2 alone forms liquid-like spherical droplets via multivalent electrostatic interactions and with isotropic mobility. Crowded environments and DNA promote MeCP2 LLPS and slow down MeCP2 mobility. DNA methylation, however, restricts the growth of heterochromatin compartments correlating with immobilization of MeCP2. Furthermore, MeCP2 self-interaction is required for LLPS and is disrupted by Rett syndrome mutations. In summary, we modelled the in vivo heterochromatin compartmentalization as well as MeCP2 concentration and heterogeneous motion using a minimal in vitro system.

About the speaker

M. Cristina Cardoso holds the chair of Cell Biology and Epigenetics at the Department of Biology of the Technical University of Darmstadt, Germany. She obtained her PhD on phage molecular genetics from the New University of Lisbon, Portugal under the supervision of Prof. Dr. Luis Archer and Prof. Dr. Herminia de Lencastre at the Gulbenkian Institute of Science, Oeiras, Portugal and at the Max Planck Institute for Molecular Genetics, Berlin, Germany. In 1991, she joined Prof. Dr. Bernardo Nadal-Ginard at the Children’s Hospital, Harvard Medical School, Boston, USA, where she worked on inducing retrodifferentiation in terminal differentiated mammalian cells. During this time, she started to explore the interplay between the mammalian cell nucleus landscape and (epi)genome metabolism. In 1995, she became a research group leader at the Franz Volhard Clinic (Charité-Berlin, Germany) and from 1997 to 2008 at the Max Delbrück Center for Molecular Medicine (Berlin). Since 2008, she has established her group at the Technical University of Darmstadt (Germany).

With her team they investigate how the mammalian (epi)genome is maintained throughout cell divisions and how the epigenetic information is translated into spatial chromatin structure and activity during differentiation, reprogramming and disease. For that, they make use of a variety of biochemical, molecular and cell biological methods with particular emphasis on advanced live-cell and super-resolution fluorescence microscopy.

Video link: http://www.cardoso-lab.org/video/CC_intro_final.mp4

Lab web page: http://www.cardoso-lab.org

Contact info: saskia<dot>lesire<at>kuleuven<dot>be