Navigation Links
New mechanism for essential genome-wide gene silencing identified

Most of the time in most cells of the body, the great majority of genes are silenced, locked away within the compacted but orderly material that makes up chromosomes. Estimates are that only about 10 percent of the roughly 25,000 genes in the human genome are activated, or "on," at any given time in a particular cell ?the default setting for most genes is "off," or repressed.

Reliable gene silencing is vital to the health of an organism. Improperly activated genes can and do lead to cancer, for example. Gene silencing is also thought to protect the genome from viruses and other potentially damaging entities, thus preserving genetic integrity.

In a new study, researchers at The Wistar Institute and colleagues have identified an important new global mechanism for this essential gene silencing, or gene repression. A report on the findings appears in the April 15 issue of Genes & Development.

"We've discovered what looks to be an evolutionarily ancient mechanism for broadly repressing and protecting the genome," says Shelley L. Berger, Ph.D., the Hilary Koprowski Professor at The Wistar Institute and senior author on the study. "We believe it to be the first identified mechanism of its kind."

The new mechanism centers on histones, relatively small proteins around which DNA is coiled to create structures called nucleosomes. Compact strings of nucleosomes, then, form into chromatin, the substructure of chromosomes.

In the study, conducted in a type of yeast called Saccharomyces cerevisiae, the scientists showed that a protein called SUMO binds to histones and acts to repress transcription of genes, and it does so at many different sites across the genome. While several other histone-related mechanisms have been identified for activating genes in yeast, this is the first one recognized as repressing gene transcription.

The finding is significant because gene-regulation strategies first observed yeast and other lower-orde r organisms are often found in mammalian cells also, including humans. In an indication of their fundamental nature, critical genetic systems are frequently conserved with few changes in life forms that diverged during evolution millions of years ago.

"In our experiments, we saw SUMO binding to histones across the genome, suggesting that if this mechanism went wrong, it could have a dramatic effect," says Berger. "We know, for example, that histones are important in a number of cancers, and SUMO may be a significant part of that."

The research team also noted a dynamic interplay between the addition of a SUMO protein to a histone ?sumoylation ?and the addition of either an acetyl group or a ubiquitin protein to a histone. The processes appear to be mutually exclusive.

"Acetylation and ubiquitylation have both been shown in earlier studies to activate gene expression," says Kristin Ingvarsdottir, co-lead author on the Genes & Development study. "Sumoylation, on the other hand, is involved in gene repression, so it makes sense that it might exist in an either/or relationship with acetylation or ubiquitylation."

Another observation made during the study was that slightly higher levels of sumoylation occur near the tips of the chromosomes, the telomeres, which are known to play a central role in maintaining genomic stability. Instability in the telomeres has been linked to aging in humans and an elevated risk for aging-related diseases, the most prominent of which is cancer.


Source:The Wistar Institute

Related biology news :

1. A new mechanism of regulating RNA degradation
2. Plants, animals share molecular growth mechanisms
3. PET/MRI scans may help unravel mechanisms of prenatal drug damage
4. Researchers discover molecular mechanism that desensitizes us to cold
5. Chemists identify immune system mechanism for methamphetamine binges
6. Key mechanism in genetic inheritance during cell division identified
7. Researchers unlock mechanism creating jigsaw puzzle-like plant cells
8. Mouse gene shows new mechanism behind cardiac infarction in man
9. UCSD research reveals mechanism involved with type of fatal epilepsy
10. Ancient immune defense mechanism is no match for HIV-1
11. Malaria mechanism revealed
Post Your Comments:

(Date:11/9/2015)... 2015 ... "Global Law Enforcement Biometrics Market 2015-2019" ... ) has announced the addition ... Market 2015-2019" report to their offering. ... ) has announced the addition of ...
(Date:11/2/2015)... Calif. , Nov. 2, 2015  SRI International ... million to provide preclinical development services to the National ... contract, SRI will provide scientific expertise, modern testing and ... variety of preclinical pharmacology and toxicology studies to evaluate ... --> The PREVENT Cancer Drug Development Program ...
(Date:10/29/2015)... 2015 Daon, a global leader in mobile ... a new version of its IdentityX Platform , ... America have already installed IdentityX v4.0 and ... FIDO UAF certified server component as an ... FIDO features. These customers include some of the largest ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... , November 25, 2015 ... Report is a professional and in-depth study on ...      (Logo: ) , ... the industry including definitions, classifications, applications and industry ... for the international markets including development trends, competitive ...
(Date:11/24/2015)... , Nov. 24, 2015 Halozyme Therapeutics, Inc. (NASDAQ: ... in New York on Wednesday, December 2 ... Torley , president and CEO, will provide a corporate overview. ... York at 1:00 p.m. ET/10:00 a.m. PT . ... relations, will provide a corporate overview. --> th ...
(Date:11/24/2015)... -- Clintrax Global, Inc., a worldwide provider of clinical research services headquartered ... the company has set a new quarterly earnings record in Q3 ... posted for Q3 of 2014 to Q3 of 2015.   ... , with the establishment of an Asia-Pacific ... United Kingdom and Mexico , with ...
(Date:11/24/2015)... 2015 --> ... released by Transparency Market Research, the global non-invasive prenatal ... of 17.5% during the period between 2014 and 2022. ... Industry Analysis, Size, Volume, Share, Growth, Trends and Forecast ... market to reach a valuation of US$2.38 bn by ...
Breaking Biology Technology: