Featured Research

from universities, journals, and other organizations

Proteins in histone group might influence cancer development, study shows

Date:
September 3, 2013
Source:
Ohio State University Wexner Medical Center
Summary:
Spool-like proteins called histones play a crucial role in packaging the nearly seven feet of DNA found in most human cells. It has been thought that a particular group of histone isoforms were functionally identical. This study shows that these isoforms can have distinct functions, and that they might play a role in cancer development. The results provide a new mechanism for the regulation of chromatin structure.

Spool-like proteins called histones play a crucial role in packaging the nearly seven feet of DNA found in most human cells. A new study shows that a group of histones that are thought to behave the same actually are functionally distinct proteins.

The findings by researchers at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) indicate that replication-dependent histone isoforms can have distinct cellular functions, and that changes in expression of the various isoforms might play a role in cancer development.

The study is published in the journal Nucleic Acids Research as a Breakthrough Article, placing it among the top 2-3 percent of papers presented by the journal in terms of significance and excellence.

"Replication-dependent histone isoforms have always been thought to be functionally identical, but we show that they have distinct functions, and that altering the levels of these isoforms can influence cell proliferation and tumor development," says principal investigator Mark Parthun, PhD, professor of Molecular and Cellular Biochemistry and a member of the OSUCCC -- James Experimental Therapeutics Program.

"These highly novel results provide a new mechanism for the regulation of chromatin structure, Parthun says."

Replication-dependent histones are highly expressed just before the onset of DNA replication during the cell cycle, and they are repressed when DNA replication is completed.

The genes that encode these histones are located in large clusters that can contain dozens of histone genes. "This localization in gene clusters led to the belief that these histones are regulated as a group, and that the multiple genes encoding each histone are functionally equivalent," Parthun says.

However, the proteins encoded by replication-dependent histone genes are not identical. For example, 16 genes encode the replication-dependent histone called H2A. Strikingly, these genes encode 11 distinct protein variations.

Parthun and his colleagues conducted the study using three bladder-cancer cell lines. Key findings include:

  • The abundance of replication-dependent histone H2A isoforms showed dramatic differences in bladder cancer cells vs. normal bladder cells;
  • Replication-dependent H2A isoforms were expressed at different levels in cancer cells; expression of one isoform was 10-fold higher than the others;
  • Knocking down the messenger RNA of a specific replication-dependent H2A isoform increased cell proliferation and tumorigenicity.
  • Replication-dependent H2A isoforms show evidence of individualized regulation.

Funding from the NIH/National Cancer Institute (grant CA101956, CA107106) and the Leukemia and Lymphoma Society supported this research.

Other researchers involved in this study were Rajbir Singh, Amir Mortazavi, Kelly H. Telu, Prabakaran Nagarajan, David M. Lucas, Jennifer M. Thomas-Ahner, Steven K. Clinton, John C. Byrd and Michael A. Freitas, The Ohio State University.


Story Source:

The above story is based on materials provided by Ohio State University Wexner Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. R. Singh, A. Mortazavi, K. H. Telu, P. Nagarajan, D. M. Lucas, J. M. Thomas-Ahner, S. K. Clinton, J. C. Byrd, M. A. Freitas, M. R. Parthun. Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone H2A isoforms in cell proliferation and carcinogenesis. Nucleic Acids Research, 2013; DOI: 10.1093/nar/gkt736

Cite This Page:

Ohio State University Wexner Medical Center. "Proteins in histone group might influence cancer development, study shows." ScienceDaily. ScienceDaily, 3 September 2013. <www.sciencedaily.com/releases/2013/09/130903194201.htm>.
Ohio State University Wexner Medical Center. (2013, September 3). Proteins in histone group might influence cancer development, study shows. ScienceDaily. Retrieved April 17, 2014 from www.sciencedaily.com/releases/2013/09/130903194201.htm
Ohio State University Wexner Medical Center. "Proteins in histone group might influence cancer development, study shows." ScienceDaily. www.sciencedaily.com/releases/2013/09/130903194201.htm (accessed April 17, 2014).

Share This



More Health & Medicine News

Thursday, April 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Thousands Of Vials Of SARS Virus Go Missing

Thousands Of Vials Of SARS Virus Go Missing

Newsy (Apr. 16, 2014) A research institute in Paris somehow misplaced more than 2,000 vials of the deadly SARS virus. Video provided by Newsy
Powered by NewsLook.com
Formerly Conjoined Twins Released From Dallas Hospital

Formerly Conjoined Twins Released From Dallas Hospital

Newsy (Apr. 16, 2014) Conjoined twins Emmett and Owen Ezell were separated by doctors in August. Now, nearly nine months later, they're being released from the hospital. Video provided by Newsy
Powered by NewsLook.com
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

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