Unraveling Mechanisms of Chromosome Formation (Job Dekker)

In this episode of the Epigenetics Podcast, we caught up with Job Dekker from the University of Massachusetts Medical School to talk about his work on unraveling mechanisms of chromosome formation.

In 2002, during graduate school, Job Dekker was the first author on the paper describing the chromosome conformation capture (3C) method, which revolutionized the field of nuclear architecture. In the 3C protocol, chromatin is crosslinked using formaldehyde and then digested using a restriction enzyme. After ligating the digested blunt ends of crosslinked DNA fragments together they can be analyzed using qPCR. In the next couple of years 3C was further developed and methods like 4C, 5C, and Hi-C were published. This led to the generation of genome-wide contact maps which helped understand the 3-D organization of the nucleus.

Job Dekker’s research group is also part of the 4D Nucleome initiative, which is dedicated to understanding the structure of the human genome. More recent work of the lab includes analyzing interactions between and along sister chromatids with a method called SisterC and expanding their research to organisms like dinoflagellates to learn more about the basic organization principles of the genome.

In this episode, we discuss the story behind the idea of the chromosome conformation capture method, how close Job Dekker was to giving up on it, how the 3C methods evolved, the importance of data visualization, and we touch on parts of his current work on dinoflagellates.

References

• Job Dekker, Karsten Rippe, … Nancy Kleckner (2002) Capturing Chromosome Conformation (Science) DOI: 10.1126/science.1067799
• Josée Dostie, Todd A. Richmond, … Job Dekker (2006) Chromosome Conformation Capture Carbon Copy (5C): A massively parallel solution for mapping interactions between genomic elements (Genome Research) DOI: 10.1101/gr.5571506
• Erez Lieberman-Aiden, Nynke L. van Berkum, … Job Dekker (2009) Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome (Science) DOI: 10.1126/science.1181369
• Amartya Sanyal, Bryan R. Lajoie, … Job Dekker (2012) The long-range interaction landscape of gene promoters (Nature) DOI: 10.1038/nature11279
• Marlies E. Oomen, Adam K. Hedger, … Job Dekker (2020) Detecting chromatin interactions between and along sister chromatids with SisterC (Nature Methods) DOI: 10.1038/s41592-020-0930-9 • Job Dekker, Andrew S. Belmont, … 4D Nucleome Network (2017) The 4D nucleome project (Nature) DOI: 10.1038/nature23884 • The 4D Nucleome Project

Related Episodes

• Hi-C and Three-Dimensional Genome Sequencing (Erez Lieberman Aiden)
• Identification of Functional Elements in the Genome (Bing Ren)
• Biophysical Modeling of 3-D Genome Organization (Leonid Mirny)
• Epigenetics and X-Inactivation (Edith Heard)
• Dosage Compensation in Drosophila (Asifa Akhtar)

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