3D Genome Origami

Scientists call for unified standards in 3D genome and epigenetic data

Studying the three-dimensional structure of DNA and its dynamics is revealing a lot of information about gene expression, expanding our knowledge of how cells, tissues and organs work in health and disease. To properly produce and manage this amount of data we need unified standards and guidelines, LifeTime researchers say.

Just like a map of the world is more than a list of places and street names, the genome is more than a string of letters. A complex choreography of proteins and nucleic acids interact differentially over time in the DNA. This lets cells selectively manage the flow of genetic information during their development and differentiation or in response to physiological and environmental triggers.

The dynamics of DNA's three-dimensional organization inside the nucleus plays a important role in this process. New techniques allow researchers to map these structural differences between cell types to explore what exactly happens during gene expression in health or disease and to understand how the DNA is organized within the tiny nucleus.

“We know that genome folding and its dynamics modulates gene expression and new technologies allow us to build 3D models to study these changes, which is currently shaking up genome research and boosting our understanding of the cell nucleus complexity,” explains Professor Marc A. Marti-Renom of the Centro Nacional de Análisis Genómico of the Centre for Genomic Regulation in Barcelona, Spain. “This is an absolutely promising field and we would like to call for standards since the rapid development of methods and the increasing complexity of data pose many challenges that must be addressed now,” he states.

Part of the LifeTime initiative for a new FET Flagship

In a perspective article published in the current issue of Nature Genetics, leading scientists in the field of dynamics and structural genomics have called for standards in 3D genome and epigenetic data. They describe the main challenges in this field and provide guidelines to think about strategies for shared standardized validation of data sets and models. This paper is a result of their experience in the 4D Nucleome Initiative as part of the LifeTime initiative for a new FET-Flagship in Europe.

About the 4D Nucleome and the LifeTime Initiatives

 

The 4D Nucleome Initiative aims to decipher the structure-function relationships of the cell nucleus as a complex biological system at all levels, from molecules to entire genomic and epigenomic landscapes, as they respond and adapt to environmental changes, as well as changes during development, cell reprogramming and ageing.

The 4D Nucleome Initiative is one of the pillars of the larger LifeTime Initiative that calls for a new FET-Flagship in Europe to understand how genomes function within cells, and how cells form tissues and dynamically remodel their activities when tissues progress towards disease.

With this call for standards, international experts at the Institut Curie in Paris, MRC Institute of Genetics and Molecular Medicine at Univeristy of Edinburgh, the Centre de Biologie Intégrative at the University of Toulouse, the Institute of Human Genetics in Montpellier, the Babraham Institute in Cambridge, the Florida State University in Florida (US), the Friedrich Miescher Institute for Biomedical Research in Basel, the Napoli University, the Berlin Institute of Health, the Institute for Research in Biomedicine IRB Barcelona, the Max Delbrück Center for Molecular Medicine in Berlin, the Institute for Epigenetics and Stem Cells Helmholtz Zentrum München in Munich, and the Centro Nacional de Análisis Genómico of the Centre for Genomic Regulation (CNAG-CRG) in Barcelona, want to ensure that information is properly characterized, validated and shared, and that resources are efficiently used.

Further information

Literature

MA. Marti-Renom et al. (2018): “4D Nucleome: challenges and guidelines towards data and model standards.” Nature Genetics 50DOI: 10.1038/s41588-018-0236-3