Job Dekker

Tuesday, 25 April 2017 at 11:00 | Large Operon, EMBL Heidelberg

Job Dekker | University of Massachusetts Medical School (USA)

Host: Yad Ghavi Helm, Genome Biology Unit

Abstract

Dynamics of chromosome folding

The 3D organisation of the genome is critical for gene regulation, genome stability and faithful transmission of chromosomes to daughter cells. We apply Chromosome Conformation Capture-based technologies to determine the principles that drive the spatial folding of genomes. I will discuss how chromosomes are folded in interphase nuclei. At the nuclear level, chromosomes are compartmentalised into large multi-Mb domains that are either active and open or inactive and closed, referred to as A and B compartments respectively. These compartments themselves are composed of smaller sub-Mb Topologically Associating domains (TADs) (Dixon et al. 2012, Nora et al. 2012). Finally, long-range gene regulation occurs within TADs through long-range looping interactions between genes and regulatory elements. Though we can now routinely obtain detailed maps of genome structure, these maps do not reveal the biophysical and dynamic properties of the interactions that build and maintain the 3D genome. I will present a new experimental approach that we have developed to quantify the stability of long-range chromatin interactions. Using this assay we find that one stable interaction or multiple dynamic interactions occur only every 20-50kb or so. Interestingly, A- and B- type interactions display different dynamics with B-type compartments being held together by more interactions and/or more stable interactions. Interestingly, this assay also reveals that specific looping interactions are highly dynamic as well. Combined these studies reveal a stably folded 3D genome that is held together by highly dynamic interactions.

Biography

Dr. Dekker received his undergraduate and graduate training at Utrecht University, The Netherlands. During his post-doctoral studies in the laboratory of Dr. Nancy Kleckner at Harvard University he developed the chromosome conformation capture technology to probe the structure of chromosomes. He is currently a Professor and Co-director of the Program in Systems Biology at the University of Massachusetts Medical School. Dr. Dekker is an Investigator of the Howard Hughes Medical Institute.

Research statement

Dr. Dekker studies the roles of the three-dimensional arrangement of chromosomes in processes such as transcription regulation, chromosome segregation and genome stability. He and his group have invented the Chromosome Conformation Capture method, as well as several high-throughput adaptations of this approach including 5C and Hi-C, that are used to determine the three-dimensional folding of chromosomes at unprecedented resolution. His laboratory also develops and applies computational methods and tools for analysis of large-scale data on chromosome structure. His research has revealed new insights into the mechanisms of long-range gene regulation by distal enhancers, the compartmentalisation of chromatin in distinct functional domains, the internal organisation of the chromatin fiber, the structure of mitotic chromosomes, and the overall organisation of entire genomes inside the nucleus.