Researchers uncover new role of heterochromatin in maintaining chromosomal integrity

Researchers uncover new role of heterochromatin in maintaining chromosomal integrity

March 04, 2019 0 Comments

A team led by researchers at Osaka University finds that extra-tight packaging of genomic material helps prevent large chromosomal rearrangements that can lead to cancer.

Although many people are aware that chromosomal damage and shortening contribute to the aging process, understanding how chromosomal defects occur is about more than just finding a way to turn back the clock. Large changes in the structure of chromosomes, known as gross chromosomal rearrangements, can result in cell death or genetic diseases such as cancer.

Heterochromatin is a more densely-coiled version of chromatin, the mass of DNA and proteins that forms chromosomes. A unique region of a chromosome called the centromere is vital for correct segregation of chromosomes during cell division. While researchers have long known that centromeres are composed of heterochromatin, why the centromere is so tightly packed and how this helps stabilize the region has remained elusive—until now.
In a recent paper published in Communications Biology, a research team led by Osaka University has uncovered the role of heterochromatin in maintaining chromosomal integrity.

Centromeric regions contain a large number of short, repeated DNA sequences. These repeats make the centromere especially susceptible to breakage and rearrangements, often causing one entire arm of a chromosome to be lost while the other arm is duplicated, forming structures called isochromosomes. But the team from Osaka University found that a specific feature of heterochromatin, histone H3 lysine 9 (H3K9) methylation, suppresses gross chromosomal rearrangements caused by centromere repeats.

"Deletion of Clr4, the protein responsible for H3K9 methylation in model organism Schizosaccharomyces pombe, caused an increase in the formation of isochromosomes with breakpoints located in the centromere repeats," says lead author Akiko Okita, suggesting that methylation helps prevent rearrangements.
However, further investigation revealed that the mechanism was even more intricate than first thought.

Heterochromatin silences the action of RNA polymerase II, an enzyme responsible for copying DNA into RNA transcripts. Unexpectedly, complete silencing of RNA transcription did not seem to be necessary to suppress gross chromosomal rearrangements. Transcription factor Tfs1/TFIIS is needed to restart RNA polymerase II if it backtracks along the already-copied DNA sequence. Intriguingly, the researchers found that deletion of Tfs1/TFIIS was sufficient to bypass the need for Clr4 in the suppression of gross chromosomal rearrangements, and that RNA transcription levels were largely unaffected by the Tfs1/TFIIS deletion.

"The results showed that repression of Tfs1/TFIIS-dependent 'persistent' transcription of centromere repeats is the key role of heterochromatin in the suppression of gross chromosomal rearrangements," explains corresponding author Takuro Nakagawa. Essentially, heterochromatin stops the repeats from being copied and used in the formation of gross chromosomal rearrangements.
"We predict that our findings will help develop methods of securing genome integrity by manipulating chromatin status rather than by changing the DNA sequence," says Dr Nakagawa. "This would be a huge accomplishment because the ability to suppress gross chromosomal rearrangements is integral to the prevention of diseases arising from chromosomal instability."




Also in Industry News

Hirschsprung's Disease Genetic Analysis Reveals Mix of Common, Rare Risk Variants
Hirschsprung's Disease Genetic Analysis Reveals Mix of Common, Rare Risk Variants

May 24, 2019 0 Comments

NEW YORK (GenomeWeb) – Genetic factors that contribute to a highly heritable developmental condition called Hirschsprung's disease include a complex suite of risk variants, ranging from common polymorphisms in non-coding elements to rarer coding variants and copy number variants (CNVs), according to new research from investigators at Johns Hopkins University, the University of Washington, the Broad Institute, and New York University. "In our study, we found that the risk of the complex phenotype...

Read More

Correction to: Modulation of lipolysis and glycolysis pathways in cancer stem cells changed multipotentiality and differentiation capacity toward endothelial lineage
Correction to: Modulation of lipolysis and glycolysis pathways in cancer stem cells changed multipotentiality and differentiation capacity toward endothelial lineage

May 24, 2019 0 Comments

In the publication of this article [1], there is an error in one of the contributing author names. The error: ‘Jalal Abdolali Zade’ Should instead read: ‘Jalal Abdolalizadeh’ Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, prov...

Read More

Protein Expression: basic concepts to new directions
Protein Expression: basic concepts to new directions

May 24, 2019 0 Comments

Date: Tuesday, 11 June, 2019 Time: 09:30  – 13:00 Place: Fèlix Serratosa,  Parc Cientific de Barcelona (PCB) This short workshop will describe many aspects of heterologous expression in E.coli, from choice of construct design through to methods to improve the levels of soluble expression and options for co-expression. In addition, it will also address expression in eukaryotic hosts, including secreted proteins and ECDs, and options for co-expression. The workshop will finish with a discussion an...

Read More