Featured Research

from universities, journals, and other organizations

Super-enhancers improve dialog between genes, disease

Date:
October 10, 2013
Source:
Whitehead Institute for Biomedical Research
Summary:
Having recently discovered a set of powerful gene regulators that control cell identity in a few mouse and human cell types, scientists are now showing that these regulators — which they named “super-enhancers” — act across a vast array of human cell types and are enriched in mutated regions of the genome that are closely associated with a broad spectrum of diseases.

This schematic depicts the pivotal role super-enhancers, seen on the far left, play in controlling key cell identity genes in embryonic stem cells (ESCs). The model shows an interconnected autoregulatory loop consisting of transcription factors that meet three criteria: 1) their genes are driven by super-enhancers, 2) they co-occupy their own super-enhancers as well as those of the other transcription factor genes in the circuit, and 3) they play essential roles in regulation of ESC state. New research from the lab of Whitehead Member Richard Young shows that super-enhancers act in similar fashion in nearly 100 different human cell types and tissues.
Credit: Courtesy Cell Press

Having recently discovered a set of powerful gene regulators that control cell identity in a few mouse and human cell types, Whitehead Institute scientists are now showing that these regulators -- which they named "super-enhancers" -- act across a vast array of human cell types and are enriched in mutated regions of the genome that are closely associated with a broad spectrum of diseases.

The findings, published online today by the journal Cell, suggest that these super-enhancers, first described in Cell several months ago by Whitehead Member Richard Young, could ultimately play important roles in disease diagnostics and therapeutics.

In April, Young reported that while the total number of genetic control elements is likely in the millions, only a few hundred super-enhancers regulate the key genes that give each cell its unique properties and functions. At the time, Young hinted that the discovery, which was based on work primarily in embryonic stem cells, would help to solve the regulatory circuitry of all human cells. This latest research represents a significant step toward that goal, producing a catalog of super-enhancers in nearly 100 human cell and tissue types.

"We've gone from a few cells to a broad swath of human cell types to create this resource and make it available to the biomedical research community," says Young, who is also a professor of biology at MIT.

Young notes that the striking finding of the new study is that beyond their roles in control of healthy cells, super-enhancers are involved in regulating the function -- and dysfunction -- of diseased cells.

"We were surprised that for so many different diseases, mutations associated with the disease occur in super-enhancers" says postdoctoral scientist Brian Abraham, an author of the study. Indeed, he and other researchers in Young's lab found in disease-relevant cell types genetic mutations associated with Alzheimer's disease, diabetes, and many autoimmune diseases in genomic regions under the control of specific super-enhancers.

The researchers also found super-enhancers operating in particularly insidious fashion across a broad spectrum of cancers, observing cancer cells assembling their own super-enhancers to overproduce malevolent oncogenes that drive such cancer hallmarks as hyperproliferation, invasion, and metastasis. Young believes that identifying, mapping, and disrupting super-enhancers could alter the way cancers are managed in the clinic.

"When we focus on personalized medicine for cancer patients, super-enhancers could serve as useful biomarkers for tracking and understanding the evolution of a person's cancer," says Young. "Ultimately, super-enhancers may well become important targets for therapeutic intervention."


Story Source:

The above story is based on materials provided by Whitehead Institute for Biomedical Research. The original article was written by Matt Fearer. Note: Materials may be edited for content and length.


Journal Reference:

  1. Denes Hnisz, Brian J. Abraham, Tong Ihn Lee, Ashley Lau, Violaine Saint-Andrι, Alla A. Sigova, Heather Hoke, Richard A. Young. Super-enhancers in the control of cell identity and disease. Cell, October 2013

Cite This Page:

Whitehead Institute for Biomedical Research. "Super-enhancers improve dialog between genes, disease." ScienceDaily. ScienceDaily, 10 October 2013. <www.sciencedaily.com/releases/2013/10/131010124351.htm>.
Whitehead Institute for Biomedical Research. (2013, October 10). Super-enhancers improve dialog between genes, disease. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2013/10/131010124351.htm
Whitehead Institute for Biomedical Research. "Super-enhancers improve dialog between genes, disease." ScienceDaily. www.sciencedaily.com/releases/2013/10/131010124351.htm (accessed September 20, 2014).

Share This



More Plants & Animals News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: San Diego Zoo Welcomes Cheetah Cubs

Raw: San Diego Zoo Welcomes Cheetah Cubs

AP (Sep. 20, 2014) — The San Diego Zoo has welcomed two Cheetah cubs to its Safari Park. The nearly three-week-old female cubs are being hand fed and are receiving around the clock care. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Chocolate Museum Opens in Brussels

Chocolate Museum Opens in Brussels

AFP (Sep. 19, 2014) — Considered a "national heritage" in Belgium, chocolate now has a new museum in Brussels. In a former chocolate factory, visitors to the permanent exhibition spaces, workshops and tastings can discover derivatives of the cocoa bean. Duration: 01:00 Video provided by AFP
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) — The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) — A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) 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