Navigation Links
Novel enzyme offers new look at gene regulation

Scientists at the University of North Carolina at Chapel Hill have purified a novel protein and have shown it can alter gene activity by reversing a molecular modification previously thought permanent.

In the study, the authors showed that a protein called JHDM1A is able to remove a methyl group from histone H3, one of four histone proteins bound to all genes. Until just last year, the addition of a methyl group to a histone had been regarded as irreversible.

"That histones can become methylated has been known for over three decades, and just now we're learning that those methyl groups can also be removed," said Dr. Yi Zhang, the lead author.

Zhang is professor of biochemistry and biophysics at UNC's School of Medicine and the university's first Howard Hughes Medical Institute investigator. He also is a member of the UNC Lineberger Comprehensive Cancer Center.

The new study is now online in the journal Nature.

"Human genes are so tightly compact within the nucleus that if the DNA of a single cell were unwound and stretched, it would be a line of about two meters in length," said Zhang. "Histones are necessary to package the DNA so that it fits inside a cell's nucleus."

Because they are so intimately associated with DNA, even slight chemical alterations of histones can have profound effects on nearby genes. Depending on the precise location and how many methyl groups are added, their presence can either switch affected genes on or off.

The first enzyme to remove methyl groups from histones, or histone demethylase, was identified last year. This was a breakthrough in the study of histone modifications, but Zhang thought pieces of the puzzle were still missing.

"We hypothesized that there were more demethylase enzymes out there for two reasons," Zhang said. "For one, the previous demethylase identified, called LSD1, could not remove a chain of three methyl groups from a histone, or a trimethyl group. Secon dly, common baker's yeast does not have LSD1, although it does have proteins adding methyl groups to histones."

Zhang devised a biochemical strategy to isolate proteins that could remove methyl from histones inside a test tube. The result was the identification of a novel protein, JHDM1A, named for JmjC histone demethylase 1A. A similar protein exists in baker's yeast and has the potential to remove trimethyl groups.

JmjC is only a section of the entire JHDM1A protein, but is required for its demethylase activity. The authors showed that disruption of JmjC prevents JHDM1A from removing histone methyl groups.

Importantly, the JmjC section of JHDM1A, or "JmjC domain," can be found in other proteins, even when the proteins share little else in common. Database searches predict more than 100 total proteins found in organisms as diverse as bacteria and man contain the JmjC domain. This suggests that many other proteins may act similarly to methyl groups from histones or other proteins.

The implications of the new findings are as diverse as the proteins that contain a JmjC domain. For example, hair loss occurs in individuals with mutations in the JmjC domain of a protein called "hairless," possibly due to defects in the appropriate removal of histone methyl groups.

"Given the large numbers of JmjC domain-containing proteins that exist in diverse organisms ranging from yeast to human, our discovery will keep many people in the field busy for the years to come," said Zhang.


Source:University of North Carolina School of Medicine

Related biology news :

1. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
2. Novel technology detects human DNA mutations
3. Novel antiviral technology inhibits RSV infection in mice
4. Novel Enzyme Shows Potential As An Anti-HIV Target
5. Novel Therapy Tested in Mice Could Chase Away Cat Allergies
6. Discovery Could Lead To Novel Approaches In HIV Treatment
7. Novel ultrafast laser detection of cancer cells also may improve understanding of stem cells
8. Research Using Mouse Models Reveals A Novel Key Player In The Initiation Of Colon Cancer
9. Novel gene-silencing nanoparticles shown to inhibit Ewings sarcoma
10. Novel live reporting system to track cells
11. Field of beams - Novel system uses polarized light pulses to reveal crop health
Post Your Comments:

(Date:11/12/2015)... Nov. 12, 2015  A golden retriever that stayed ... dystrophy (DMD) has provided a new lead for treating ... the Broad Institute of MIT and Harvard and the ... . Cell, pinpoints a protective ... the disease,s effects. The Boston Children,s lab of ...
(Date:11/11/2015)... Minn. , Nov. 11, 2015   MedNet Solutions ... entire spectrum of clinical research, is pleased to announce that ... in Clinical Trials (PCT) event, to be held November ... be able to view live demonstrations of iMedNet ... and learn how iMedNet has been able to ...
(Date:11/9/2015)... , Nov. 09, 2015 ... the addition of the "Global Law ... their offering. --> ) ... "Global Law Enforcement Biometrics Market 2015-2019" ... Research and Markets ( ) has ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... November 24, 2015 , ... In harsh ... Insertion points for in-line sensors can represent a weak spot where leaking process ... series of retractable sensor housings , which are designed to tolerate extreme process ...
(Date:11/24/2015)... -- Capricor Therapeutics, Inc. (NASDAQ: CAPR ... and commercialization of first-in-class therapeutics, today announced that ... to present at the 2015 Piper Jaffray Healthcare Conference ... The Lotte New York Palace Hotel in ... --> . --> ...
(Date:11/24/2015)... ... ... Whitehouse Laboratories is pleased to announce that it has completed construction on ... to basic USP 61, USP 62 and USP 51 testing specific to raw materials ... micro testing performed by one supplier. Management has formally announced that the ...
(Date:11/23/2015)... HONG KONG, Nov. 23, 2015 China Cord ... "Company"), China,s leading provider of cord blood collection, laboratory ... services, today announced its preliminary unaudited financial results for ... 2016 ended September 30, 2015. --> ... Highlights , Revenues for the second quarter of ...
Breaking Biology Technology: