New research published online in Nature by the team of Edith Heard, PhD, from the Curie Institute and Job Dekker, PhD, from the University of Massachusetts Medical School (UMMS), reveals a new layer in the complex organization of chromosomes. The scientists have shown that chromosomes fold in a series of contiguous "yarns" that harbor groups of genes and regulatory elements, bringing them in contact with each other and allowing them to work in a coordinated manner during development.
Chromosomes are relatively large molecules that, when spread out, can measure up to the length of an entire human arm. Despite their size, however, they are actually confined within the small space of the cell nucleus which is just a few micrometers in size. Furthermore, within each cell nucleus are multiple chromosomes. In humans, for example, there are 23 pairs of chromosomes. In order to fit all this material into this small area, chromosomes are folded, compacted and mingled in the three-dimensional space of the nucleus.
So do chromosomes fill the nucleus just like spaghetti fills a plate? "Not quite," said Elphege Nora, PhD, a post-doctoral fellow on the team of Dr. Heard, head of the Genetics and Developmental Biology Lab at the Curie Institute. "Chromosome folding follows a pattern, and this actually turns out to be important for ensuring their proper function."
A chromosome looks like a series of tiny yarns
"We have known for decades that the DNA of individual genes is wrapped around nucleosomes to form the classical 'beads-on-a-string' structure," said Dekker, co-director of the Program in Systems Biology at UMMS. "Our new study now shows that these beads-on-a-string subsequently fold up to form 'yarns-on-a-string,' where each yarn is a group of genes. This domainal organization of chromosomes represents a previously unknown higher order level of folding that we believe is a fundamental organizing principle of genomes."
These globule-like yarns span anything from a few hundred thousand to a million base pairs, explained Heard. Base pairs (abbreviated as A, C, G and Ts) are the genome's unit of measurement, and a person's DNA consists of over 3 billion pairs. "The real surprise, however, lies in how this spatial folding of chromosomes links up to their functional organization," said Heard. "This chromosome folding pattern brings together, into the same 'yarn,' several genes, up to 10 of them, or even more."
However, there are not just genes in these yarns. So called "regulatory genomic elements," that can control the activity of neighboring genes like switches are also found clustered together with the genes in these chromosomal yarns. A group of genes belonging to the same yarn will therefore be likely to contact a similar set of regulatory elements, and this can result in the coordinated activity of these genes during development.
These new observations shed some light on several long-standing mysteries of genetics, such as the reason why some DNA mutations can end up affecting genes that are located thousands or even a million base pairs away.
"The cell nucleus is packed with genes, and the cell is faced with the challenge to turn on or off each one of them correctly," said Dekker. "By organizing groups of genes in isolated domains, or yarns that do not mingle or mix with other genes, the cell has solved the problem of how to regulate groups of genes coordinately and without interference from other genes."
However, damaging one of these "chromosome yarns" can lead to the misbehavior of all the genes it contains. "The three-dimensional organization of chromosomes allows distal genomic elements to be brought together and to functionally interact with each other. At certain points during development it is thus possible to precisely orchestrate the activity of genes that are far away from each other on the linear chromosome thread, but that are actually in contact physically, within a chromosome yarn," said Nora. "The down side of this type of organization is that a single mutation altering the organization of such a 'chromosome yarn' can affect a whole group of genes."Three-dimensional folding provides shortcuts through the chromosome
Beyond advancing our fundamental understanding of chromosome biology, these studies also open up new avenues for studying certain diseases, such as genetic disorders that are due to mutations in the DNA sequence which disrupt the proper activity of certain genes. Sometimes the mutation causing these defects is not directly in the gene, but affects one of its regulatory elements somewhere in its extended chromosomal neighborhood. Finding such mutations along the chromosome has been a bit like looking for a needle in a haystack because scientists did not know which genes were partnered with which regulatory elements. The hunt for such mutations can now be directed first to the chromosomal region most likely to harbor the regulatory elements of the misbehaving gene – inside the chromosome "yarn" to which that gene belongs.About the University of Massachusetts Medical School
Jim Fessenden | EurekAlert!
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Physics and Astronomy
30.03.2017 | Studies and Analyses
30.03.2017 | Life Sciences