Featured Research

from universities, journals, and other organizations

Tools used to decipher 'histone code' may be faulty

Date:
December 16, 2010
Source:
University of North Carolina School of Medicine
Summary:
Recent research has found a number of issues with histone antibodies, the main tools used to decipher this code, suggesting they may need more rigorous testing.

This is Brian Strahl, PhD, of the University of North Carolina at Chapel Hill.
Credit: UNC Medical Center News Office

The function of histones -- the proteins that enable yards of DNA to be crammed into a single cell -- depends on a number of chemical tags adorning their exterior. This sophisticated chemical syntax for packaging DNA into tight little coils or unraveling it again -- called the "histone code" -- is the latest frontier for researchers bent on understanding how genetics encodes life.

But recent research from the University of North Carolina at Chapel Hill has found a number of issues with histone antibodies, the main tools used to decipher this code, suggesting they may need more rigorous testing.

"When I have presented our findings at major meetings, the reactions of my peers have been shock and awe across the board," said senior study author Brian Strahl, PhD, associate professor of biochemistry and biophysics at UNC.

"Hundreds and hundreds of researchers around the world use them and assume they are accurate. Yet we have found that they need to be used with caution." Strahl is a member of the UNC Lineberger Comprehensive Cancer Center.

The results of the study, which appears online December 16, 2010, in the journal Current Biology, also found that the proteins that interpret the histone instructions are affected not just by the specific chemical tag they land on but also by other tags in the neighborhood.

The "Histone Code" was first proposed almost ten years ago by Strahl and epigenetics researcher C. David Allis, who was his postdoctoral advisor at the time. In a review article published in the journal Nature that has since been cited over 3000 times, Strahl and Allis suggested a model of how histones and their posttranslational modifications may function in chromatin.

Histones are the protein spools around which strands of DNA are wrapped to form a package called chromatin. Depending on the modifications or tags decorating the histones, DNA is either closed up tightly within this package or lies open so that its genes can be read.

Strahl and Allis hypothesized that distinct combinations of histone modifications work together to form a code, akin to the classic genetic code in which distinct combinations of nucleotides make an amino acid. These histone modifications -- chemical changes like phosphorylation, acetylation and methylation -- generate a language that is interpreted through the ability to recruit the proteins that modulate chromatin.

"But this histone code is way more complicated, because there are over a 100 different histone modifications, and they are working in a three-dimensional space that is very difficult to visualize," said Strahl. "We can't say that this mark or this combination of modifications will always mean a certain thing. But what I think we can say is that multiple modifications can help tip the balance of one chromatin state to another, making the underlying DNA more or less accessible to the protein machinery."

In order to uncover what some of those codes might be, the researchers started generating chunks of histone proteins, each engineered to contain various combinations of modifications. In a completely new approach to the histone code, Strahl and his colleagues printed these modified chunks or peptides onto glass slides, generating peptide arrays akin to DNA arrays.

When they tested widely used commercial antibodies that were directed against specific modifications on histones, like methylysine or methylarginine, they found the antibodies didn't always recognize the site they were supposed to, sometimes even binding to off-targets better than their intended target.

The results fit nicely with a study published recently in Nature Structural Biology by Jason Lieb, Ph.D., a professor of biology at UNC and a Lineberger Center member. Lieb used older approaches like immunofluorescence, CHIP and Western blots to show that many commercial antibodies were not performing as they should.

An additional finding of the study by Strahl and colleagues was that antibodies, as well as the proteins that naturally bind chromatin, were greatly affected by neighboring modifications.

"This result gives further support to the idea of the histone code, in that the ability of a protein to bind to histones may depend on a particular modification landscape and not just one single modification" said Strahl. "The presence of an acetylation site nearby could impact the binding of a protein at its intended phosphorylation site. So altogether these modifications generate a landscape that is vitally important in how proteins read the histone code."

The research was funded by the National Institutes of Health. Study co‑authors were Stephen Fuchs, Ph.D., a postdoctoral scientist in Strahl's lab, and Krzysztof Krajewski , a research assistant professor at UNC.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University of North Carolina School of Medicine. "Tools used to decipher 'histone code' may be faulty." ScienceDaily. ScienceDaily, 16 December 2010. <www.sciencedaily.com/releases/2010/12/101216122010.htm>.
University of North Carolina School of Medicine. (2010, December 16). Tools used to decipher 'histone code' may be faulty. ScienceDaily. Retrieved April 19, 2014 from www.sciencedaily.com/releases/2010/12/101216122010.htm
University of North Carolina School of Medicine. "Tools used to decipher 'histone code' may be faulty." ScienceDaily. www.sciencedaily.com/releases/2010/12/101216122010.htm (accessed April 19, 2014).

Share This



More Health & Medicine News

Saturday, April 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com
Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins