An integrated view of the structure and function of the human 4D nucleome
Managing Big Data in the Cell Nucleus
If your DNA is an instruction manual for almost all cellular activities, rewriting that manual may open a pathway to tailoring your genetic makeup to any needs. That possibility drives much of today’s studies of DNA.
DNA sits in the cell nucleus, but it isn’t just a loose string. DNA folds into a dynamic 3D shape to manage the most immense data storage density and scale imaginable. Understanding the processes behind this phenomenon is the goal of the 4D Nucleome (4DN) project—“nucleome” meaning a complete description of the cell nucleus in space and time analogous to genome, transcriptome, metabolome and proteome. This program funded by the National Institutes of Health brought together scientists from many organizations with the objective of understanding the 3D organization of the DNA in the nucleus and how that organization changes over time.
The latest development of the 4DN program is summarized in a manuscript titled, “An integrated view of the structure and function of the human 4D nucleome,” and published in Nature, featured on the journal’s cover.
In this paper, the researchers pay close attention to how nuclear organization affects normal development and various diseases. They studied the 3D structure of the human nucleome to see how DNA loops and folds. They discovered that the way DNA is folded helps decide when and how genes are used and found over 140,000 looping connections where distant parts of DNA touch each other in 3D. Each of these folds can affect cell behavior and possibly contribute to disease. Novel technology also helped the researchers build computer models that predict how DNA is arranged in space and how that arrangement links to gene activity.
San Diego BioMed congratulates the Gilbert Lab as contributors to the manuscript, demonstrating that when and where a chromosome segment is copied affects the structure that forms afterward. Their data also reveals some of the molecular mechanisms that link structure to function. Chromosomes are highly organized structures of manageable pieces of DNA that are wrapped around proteins. Since disruptions in chromosome organization are found in virtually all diseases, understanding the mechanisms that control their structure opens the door to correcting them, paving the way to new pathways to therapies or cures.
This international effort brought together more than 150 laboratories, unified their work into a single story that maps, analyzes, and classifies DNA interactions, plus provides guidelines for future studies.
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