Navigation Links
Large DNA stretches, not single genes, shut off as cells mature
Date:1/18/2009

Experiments at Johns Hopkins have found that the gradual maturing of embryonic cells into cells as varied as brain, liver and immune system cells is apparently due to the shut off of several genes at once rather than in individual smatterings as previous studies have implied.

Working with mouse brain and liver cells, as well as embryonic stem cells, Johns Hopkins University School of Medicine professor Andrew Feinberg, M.D., M.P.H., led an investigation of a kind of epigenetic modification to histones, the molecular "spools" that DNA winds around in the cell nucleus. This modification is a variety of the so-called epigenetic changes that alter the function of cells without directly altering the nuclear DNA in the cells.

Other scientists had previously found that histone modifications appear to silence individual genes in the DNA that coils around affected histones. But when Feinberg and his team compared the activity of thousands of genes in the liver and brain cells, they found that a particular modification in which two methyl groups clip onto histones seemed to silence long stretches of DNA containing many genes at once. The findings will publish in Nature Genetics online on Jan. 18.

Since the silenced stretches varied greatly between the different types of cells, Feinberg, postdoctoral fellow Bo Wen, and their colleagues wondered whether these sections called large organized chromatin K9 modifications, or LOCKS might be responsible for the transition from the "blank slate" quality of embryonic cells to the specialized functions that mature cells take on. To find out, he and his team looked for LOCKs in mouse embryonic stem cells. Unlike mature, adult liver and brain cells, in which about 40 percent of the genome was silenced by LOCKs, the embryonic stem cells had no LOCKs.

Next, the researchers compared the regions of DNA affected by LOCKs between mouse liver and brain cells and their corresponding human cells. The same cell types in both organisms had remarkably similar regions of DNA silenced by LOCKs, suggesting that the same genes necessary to control cell function are affected in mice and people.

"These results suggest that LOCKs appear gradually during development, refining cells' functions as they differentiate into particular cell types," Wen says. "Our experiments suggest that the whole forest of genes is changing, but people have been looking at the individual trees."

Because epigenetic changes also are known to play a role in abnormal cell growth, the researchers suspected that LOCKs were involved in the development of cancer. When they looked for genes in several common cancer cell lines often used in research, they indeed found significantly fewer LOCKs than in normal liver and brain cells.

"In cancer, some of these LOCKs may become unlocked," says Feinberg. "Sections of DNA that were silenced in a cell type might become active, giving cancer cells characteristics of other cell types that they're not supposed to have."

Feinberg says this "unlocking" might cause cancer cells to revert to a more immature developmental state, explaining some of their unusual behavior, such as extreme proliferation or migration to different areas of the body.


'/>"/>

Contact: Christen Brownlee
cbrownlee@jhmi.edu
410-955-7832
Johns Hopkins Medical Institutions
Source:Eurekalert

Related biology news :

1. Tips for making a green holiday from the worlds largest scientific society
2. Researchers solve piece of large-scale gene silencing mystery
3. Pollution at home lurks unrecognized, instead attributed to large-scale environmental disasters
4. Small satellite takes on large thunderstorms
5. Less than one month to opening of world’s largest global congress on osteoporosis
6. Paradigm Tactical Products to be Largest Distributor of Metal/Radiation Detection Wands in United States
7. Research uncovers new steps on pathway to enlarged heart
8. Yale journal finds nanomaterials may have large environmental footprint
9. Complete Genomics launches, becomes worlds first large-scale human genome sequencing company
10. Lack of large-scale experiments slows progress of environmental restoration
11. Carbon Disclosure Project: Worlds largest corporations seek clarity on climate change regulation
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/4/2017)... 2017   EyeLock LLC , a leader of ... States Patent and Trademark Office (USPTO) has issued U.S. ... of an iris image with a face image acquired ... company,s 45 th issued patent. ... given the multi-modal biometric capabilities that have recently come ...
(Date:3/30/2017)... , March 30, 2017 Trends, opportunities ... (physiological and behavioral), by technology (fingerprint, AFIS, iris recognition, ... recognition, and others), by end use industry (government and ... immigration, financial and banking, and others), and by region ... , Asia Pacific , and ...
(Date:3/24/2017)... Controller General of Immigration from Maldives Mr. Mohamed Anwar and ... international IAIR Award for the most innovative high security ePassport and eGates  ... ... Maldives Immigration Controller General, Mr. Mohamed Anwar ... right) have received the IAIR award for the "Most innovative high security ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. 11, ... Research, London (ICR) and University of ... SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma (MM), ... nine . The University of Leeds ... funded by Myeloma UK, and ICR will perform the testing ...
(Date:10/11/2017)... ... October 11, 2017 , ... A new study ... in frozen and fresh in vitro fertilization (IVF) transfer cycles. The ... IVF success. , After comparing the results from the fresh and frozen transfer ...
(Date:10/10/2017)... ... October 10, 2017 , ... San Diego-based team building and ... rebranding initiative announced today. The bold new look is part of a transformation ... moves into a significant growth period. , It will also expand its service offering ...
(Date:10/10/2017)... PA (PRWEB) , ... October 10, 2017 , ... ... City Science Center’s FirstHand program has won a US2020 STEM Mentoring Award. Representatives ... the award for Excellence in Volunteer Experience from US2020. , US2020’s mission is ...
Breaking Biology Technology: