Genome architecture caught in motion

October 09, 2017

PHILADELPHIA -- (Oct. 9, 2017) -- Researchers at The Wistar Institute have uncovered new aspects of the three-dimensional organization of the genome, specifically how the genetic material is compacted and de-compacted in a timely fashion during the different phases of the cell cycle. This study was published in Nature Structural & Molecular Biology.

"We are just starting to appreciate that the way our genome is spatially organized in our cells has a profound impact on its function," said lead author of the study Ken-ichi Noma, Ph.D., associate professor in the Gene Expression and Regulation Program at Wistar. "Deciphering the three-dimensional structure of chromatin is essential to understanding key functions like transcription, DNA replication and repair."

The genetic information contained inside each of our cells is encoded by several feet worth of DNA molecules. Such an enormous amount of genetic material is packed into a microscopic space by folding it into a highly organized complex of DNA and proteins called chromatin. Although already significantly compacted, chromatin needs to be further condensed upon entry into mitosis, the process that divides each cell into two identical cells, in order to faithfully segregate the genetic material. Just as we pack up household belongings into smaller boxes when we relocate into a new house, it is easier to move and divide the DNA in the form of compacted chromosomes. This process has been known for several decades, yet the underlying molecular mechanisms that govern chromatin condensation and de-condensation are still poorly defined.

The Noma lab has extensively studied the mechanisms of genome organization using fission yeast as a model organism because it shares some important features with human cells while having a much smaller genome.

Noma and colleagues have previously described how two protein complexes called condensin and cohesin mediate the formation of functional genome-organizing structures called topological domains by establishing contacts that bring distantly located DNA regions closer together. Specifically, cohesin mediates local contacts, forming small topological chromatin domains, whereas condensin drives longer-range contacts, organizing larger domains.

In the new study, the lab applied similar genomic methodology to dissect the condensation and de-condensation of chromatin in topological domains over time, following the formation and decay of chromatin contacts throughout the different phases of the cell cycle. They discovered that the larger domains mediated by condensin are formed during mitosis, whereas the smaller, local domains mediated by cohesin remain stable throughout the whole cycle.

"Contrary to what was generally assumed in the field, we find that condensation and de-condensation of the chromatin domains happen very gradually and the cells oscillate smoothly between more and less condensed chromatin states," said first author of the study Hideki Tanizawa, Ph.D., an associate staff scientist in the Noma lab.

Alterations of the three-dimensional structures of the genome are linked to genetic diseases and cancer, presenting a powerful example of how basic cellular processes are relevant for disease. "The field is still in an early discovery phase but our study adds new insight into a fundamental biological process that may assist the development of novel therapeutic strategies in the future," added Noma.
-end-
This work was supported by the National Institutes of Health/National Institute of General Medical Sciences grant R01GM124195, the NIH Director's New Innovator Award Program grant DP2-OD004348 and by the G. Harold & Leila Y. Mathers Charitable Foundation. Core support for The Wistar Institute was provided by the Cancer Center Support Grant (CCSG) CA010815.

Co-authors of this study from The Wistar Institute include Kyoung-Dong Kim and Osamu Iwasaki.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.

The Wistar Institute

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.