Genetic material, located within the nucleus of a cell, is not randomly organized. Although the spatial configuration of DNA and DNA-associated proteins is known to influence gene expression and cellular function, how this occurs is currently unknown. The Common Fund’s 4D Nucleome program aims to understand the principles behind the three-dimensional organization of the nucleus in space and time (the 4th dimension), the role nuclear organization plays in gene expression and cellular function, and how changes in the nuclear organization affect normal development as well as various diseases.
Elaborate X-inactivated Chromosome Structure Revealed
X-inactivation is the process by which one of the two X chromosomes present in female mammals is inactivated. Although the inactivated X chromosome appears to be a condensed blob under a microscope, a new study from 4D Nucleome grantee Job Dekker, Ph.D. and collaborators reveals a highly elaborate structure. Using a variety of methods, including chromosome conformation capture technologies and mouse models, they found that the inactive X chromosome is actually composed of two highly organized structures. Read the full highlight here.
In the news - Read the press release from the University of Massachusetts Medical School here.
Bursting onto the Transcription Scene
There are hundreds of thousands of enhancers in the human genome, many of which precisely regulate patterns of gene expression that are required for the differentiation and growth of cells and tissues. To better understand the relationship between transcriptional bursts and enhancers, Dr. Michael Levine, a 4D Nucleome grantee, used quantitative analysis and live-imaging methods in Drosophila embryos in real time. Their results suggests the importance of chromosome architecture in control of gene expression. Read the full highlight here.
In the news - Gene expression: Dynamic enhancer-promoter interactions for transcriptional bursting.
NEW Congratulations to Dr. Clodagh O'Shea, a 4D Nucleome grantee recently named as a Howard Hughes Medical Institute faculty scholar. Dr. O'Shea is working to "identify critical 3D genomic interactions that are subverted in both viral infection and cancer and the rational design of powerful synthetic viral therapies for the treatment of patients suffering from cancer". Read more about this award here. Read the Salk Institute press release here.
Conversations: A guide to packing your DNA. In a conversation with Cell, 4D Nucleome grantees Drs. Job Dekker, Mitchell Guttman, and Stavros Lomvardas discuss the organization of genetic material in the nucleus, how it occurs, and why it matters. Learn more about this conversation here.
4D Nucleome investigator featured on "Science Happens!" Watch Dr. Job Dekker describe how the folding of DNA strands holds cues to human health. See the video below and learn more about this episode here.
Seeing transcription in a new light
"Imaging Transcription: Past, Present, and Future" : 4D Nucleome investigator Dr. Robert H Singer and collaborators provide an overview of the evolution and current state of transcription imaging technologies. Also discussed are important concepts and possible future developments that might solve long standing questions in transcriptional regulation and gene expression.
"Unraveling nuclear architecture" named a 2016 Method to Watch. The mapping of nuclear architecture was named a Nature Methods 2016 Method to Watch, with special mention of the 4D Nucleome program. Read the full story here.
4DN Program Awardees Announced
Approximately $25 million has been awarded to 29 research teams to support the development of new mapping and imaging tools, novel computational tools, pilot mapping of the 3D organization of mammalian genomes, and studies to understand and manipulate nuclear architecture. Learn more about these awards here.
Read the press release announcing the launch of 4D Nucleome and other Common Fund programs designed to take aim at gaps in biomedical research.
Contact us at: 4DNucleome@mail.nih.gov