Featured Research

from universities, journals, and other organizations

Knowledge Of Epigenetics Helps Scientists Develop Tool To Study Deadly Parasite’s Histone Code

Date:
May 25, 2009
Source:
Rockefeller University
Summary:
In the Japanese art of paper folding, a series of folds can make the same sheet of paper into a ballerina or baby elephant. But try unfolding the baby elephant and making it into a ballerina. It's like trying to make a neuron from a kidney cell. Epigenetics, it turns out, isn't much different from this old Japanese art: Each fold, or epigenetic crease, both limits and permits further potential folds in a way that mirrors how epigenetic changes seal a cell's fate.

In the Japanese art of paper folding, a series of folds can make the same sheet of paper into a ballerina or baby elephant. But try unfolding the baby elephant and making it into a ballerina. It’s like trying to make a neuron from a kidney cell. Epigenetics, it turns out, isn’t much different from this old Japanese art: Each fold, or epigenetic crease, both limits and permits further potential folds in a way that mirrors how epigenetic changes seal a cell’s fate.

The changes occur on the tails of histones, the globular proteins around which DNA winds itself to make chromatin, the stuff of chromosomes. When the strings of amino acids that make up the tails undergo epigenetic modifications — chemical alterations such as methylation or acetylation — chromatin’s structure changes in order to either seal off DNA or make it available for transcription. Like each fold of the paper, each modification ultimately shapes chromatin’s structure.

In a genome-wide study led by George A.M. Cross, head of the Laboratory of Molecular Parasitology, and T. Nicolai Siegel, a graduate student in the lab, scientists at Rockefeller University have mapped epigenetic changes that are likely to play a role in initiating the transcription of genes in Trypanosoma brucei, the deadly single-celled parasite responsible for African sleeping sickness. The advance marks the first time scientists have been able to develop the tools to map these changes across the entire genome of the evolutionarily ancient parasite.

“Histones in trypanosomes are extraordinarily divergent from histones in other organisms, so we couldn’t use the same commercially available antibodies we use for mammals and yeast to isolate them and study their modifications,” says Cross. “If we were interested in histone modifications, we couldn’t reliably predict which amino acids in the histone tails would be modified and had a role in transcription. We now have the means to do that.”

Two years ago, Cross and his colleagues were the first to identify histone modifications that exist in T. brucei, focusing on modifications that occur on H4, one of the four pairs of core histones. Building off that research, Siegel was able to create an antibody specific to the modified histone, whose 10th amino acid was acetylated. When the antibody was exposed to the trypanosome genome, it attached to the modified histones, allowing Siegel to extract them — along with the DNA coiled around them — from the parasite’s nucleus.

“What I had was all these DNA fragments, which I could then map back to the genome and see every location where this modification occurred,” says Siegel.

The results were striking. This modification of H4 occurred along every probable transcription start site across the trypanosome genome, suggesting that this modification serves as a loading dock for transcription factors. The team proposes that at these transcription start sites, H4’s tail is acetylated, which helps open up chromatin to make room for factors that initiate transcription.

Siegel then decided to repeat the procedure for every histone variant (in trypanosomes, each core histone has one variant), revealing that two of them occur at transcription termination sites and two at probable transcription start sites, with the two at the start sites always occurring together.

They further found that the two variants at the start sites make the histone unstable. When histones become unstable, they are ejected from the chromatin structure and the chromatin collapses. So all that DNA that is wound tightly around the histones loosens up, becoming more accessible to factors that initiate transcription.

“The research gives us important clues about how transcription is initiated in this deadly parasite,” says Cross. “If we can block transcription, we may be able to gain the upper hand in the cat-and-mouse game this parasite plays with our immune system.”


Story Source:

The above story is based on materials provided by Rockefeller University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Siegel et al. Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei. Genes & Development, 2009; 23 (9): 1063 DOI: 10.1101/gad.1790409

Cite This Page:

Rockefeller University. "Knowledge Of Epigenetics Helps Scientists Develop Tool To Study Deadly Parasite’s Histone Code." ScienceDaily. ScienceDaily, 25 May 2009. <www.sciencedaily.com/releases/2009/05/090522171901.htm>.
Rockefeller University. (2009, May 25). Knowledge Of Epigenetics Helps Scientists Develop Tool To Study Deadly Parasite’s Histone Code. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2009/05/090522171901.htm
Rockefeller University. "Knowledge Of Epigenetics Helps Scientists Develop Tool To Study Deadly Parasite’s Histone Code." ScienceDaily. www.sciencedaily.com/releases/2009/05/090522171901.htm (accessed April 16, 2014).

Share This



More Plants & Animals News

Wednesday, April 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com
In Washington, a Push to Sterilize Stray Cats

In Washington, a Push to Sterilize Stray Cats

AFP (Apr. 14, 2014) To curb the growing numbers of feral cats in the US capital, the Washington Humane Society is encouraging residents to set traps and bring the animals to a sterilization clinic, after which they are released.. Duration: 02:29 Video provided by AFP
Powered by NewsLook.com
After Attack, Officials Kill 5 Bears in Florida

After Attack, Officials Kill 5 Bears in Florida

AP (Apr. 14, 2014) Florida wildlife officials say they have killed five bears following an attack on a woman in a suburban subdivision in central Florida. Forty-five year-old Terri Frana was attacked by a large bear in her driveway Saturday. (April 14) Video provided by AP
Powered by NewsLook.com
Uruguay Opens Its First Cannabis Library

Uruguay Opens Its First Cannabis Library

AFP (Apr. 13, 2014) Uruguay opened its first Cannabis Library in Montevideo on Saturday, where people can come and read books on cannabis or take classes on how to grow the plant or even how to cook with it. Duration: 01:20 Video provided by AFP
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