Chromatin is a complex of genomic DNA and proteins that make up the chromosomes within the nucleus of a cell. The organization of genomic material into chromatin is presumed to play an important role in regulating expression of genes. However, the precise relationship between spatial genome organization and expression of resident genes in health and disease remains unclear. Toward understanding 3D genome architecture and its relationship to gene regulation, 4D Nucleome researcher Dr. Yijun Ruan, Ph.D., a Jackson Laboratory Professor, Florine Deschenes Roux Chair and Director of Genome Sciences, and his team worked with international collaborators to identify a framework in which genes are organized and transcribed at the chromosomal level.
For these studies, the authors used advanced 3D genome mapping technologies and simulation, as well as super-resolution microscopy. These models revealed higher order chromosome folding and specific chromatin interactions, mediated by the chromatin proteins CTCF and cohesin. These chromatin structures suggest a “barrier” between genes being actively transcribed and those that are not. Importantly, these studies further uncovered potential mechanistic links between genetic mutations associated with specific disease and chromatin topology.
“The significance of this paper lies in our advanced 3D genome mapping strategy,” Dr. Ruan said, “which allowed us to reveal, for the first time, the higher-order and detailed topological structures of the human genome mediated by CTCF and cohesin, and the relation to gene transcription regulation carried out by RNA polymerase II. This publication is also timely adding new excitement to the recently initiated 4D Nucleome program by NIH." For additional information, read The Jackson Laboratory news release.
Reference
- CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription. Tang Z, Luo OJ, Li X, Zheng M, Zhu JJ, Szalaj P, Trzaskoma P, Magalska A, Wlodarczyk J, Ruszczycki B, Michalski P, Piecuch E, Wang P, Wang D, Tian SZ, Penrad-Mobayed M, Sachs LM, Ruan X, Wei CL, Liu ET, Wilczynski GM, Plewczynski D, Li G, Ruan Y. Cell. (7) 11611 – 27.
