The goal of the Common Fund’s 4D Nucleome (4DN) program is to study the three-dimensional organization of the nucleus in space and time (the 4th dimension). The nucleus of a cell contains DNA, the genetic “blueprint” that encodes all of the genes a living organism uses to produce proteins needed to carry out life-sustaining cellular functions. Scientists know that how the information in the nucleus organized, stored, and unpackaged are all important to basic human health and we are only starting to learn how changes in this organization can lead to the development of different diseases, such as cancer or our response to infectious agents like viruses.
The 4DN program has generated a variety of tools and resources so scientists can continue to learn about the importance of nuclear organization. Program deliverables currently available through the public 4DN Portal include nearly 2000 datasets from hundreds of experiments, 52 software packages and 23 protocols and reagents for researchers to use.
Pending availability of funds, the 4DN program will continue to a second stage of funding starting in 2020. The first stage of the 4DN program focused on developing ways to determine the 3D architecture of DNA in the nucleus. Stage two of the 4DN program will focus on determining what the biological meaning of this architecture is, how the organization may change in different diseases, and how we can use this information to improve human health.
The nucleus of a cell contains DNA, the genetic “blueprint” that encodes all of the genes a living organism uses to produce proteins needed to carry out life-sustaining cellular functions. It is estimated that each human cell contains approximately 2 meters (6.5 feet) of DNA, squeezed inside the cell’s microscopic nucleus. We now know that DNA is not randomly arranged within the nucleus; instead, the organization of the nucleus is tightly controlled. However, the functional consequences of this organization are not well understood. What are the principles that govern the three-dimensional architecture of the nucleus, and how does this architecture contribute to gene expression regulation? How does nuclear architecture change over time (the 4th dimension) in the course of normal development? Do dysfunctional alterations in nuclear organization lead to disease, and/or could they be used to diagnose diseases?
The Common Fund’s 4D Nucleome program aims to understand the principles underlying nuclear organization in space and time, the role nuclear organization plays in gene expression and cellular function, and how changes in nuclear organization affect normal development as well as various diseases. This program is developing technologies, resources and data to enable the study of the 4D Nucleome, including novel tools to explore the dynamic nuclear architecture and its role in gene expression programs, models to examine the relationship between nuclear organization and function in both normal development and disease, and reference maps of nuclear architecture in a variety of cells and tissues.
This program includes six initiatives:
- Nuclear Organization and Function Interdisciplinary Consortium (NOFIC): NOFIC is composed of multidisciplinary teams that are developing and validating novel approaches and genome-wide mapping technologies that will lead to a deeper understanding of nuclear organization in time and space, and the role of this organization in regulating gene expression programs.
- Nucleomics Tools: This initiative is stimulating the development and validation of chemical and biochemical technologies for measuring three dimensional interactions between specific places in the genome (genomic loci), or between genomic loci and regulators of genome organization and function, in mammalian cells.
- Study of Nuclear Bodies and Compartments: Nuclear bodies (structural and functional subunits within the nucleus) and nuclear compartments (specific subregions within the nucleus) set up distinct local environments that facilitate many important nuclear processes. This initiative supports the development of tools and strategies to study the three dimensional architecture of the nucleus in relationship to the spatial arrangement of nuclear bodies and molecular machinery regulating gene expression, the structure and function of poorly characterized nuclear structures and compartments, and the role of specialized proteins and RNAs in nuclear organization and function.
- Imaging Tools: This initiative stimulates the development of higher throughput, higher resolution and higher content imaging approaches that can measure changes in nuclear organization in live single cells.
- Organizational Hub (4DN-OH) and Opportunity Pool: The 4DN-OH developed a community website to facilitate sharing of data, reagents, standards, and protocols between 4D Nucleome investigators, and with the larger scientific community. 4DN-OH helps foster collaborations between 4D Nucleome investigators, organize yearly scientific meetings, and oversee administrative aspects of the program. 4DN-OH also administers the Opportunity Pool, a fund to support new projects and initiatives that address identified needs arising throughout the lifetime of the program.
- Data Coordination and Integration Center (4DN-DCIC): 4DN-DCIC tracks, stores, and displays all data generated by 4D Nucleome investigators. It provides a Data Analysis Center to assist with integrated analyses, develops metrics and standards to be adopted by the community at large, and provides visualization tools to facilitate access and understanding of complex datasets.
Download the program flyer.
This page last reviewed on July 22, 2019