Navigation Links
A foot in the door to genetic information
Date:3/7/2012

In the cell nucleus, DNA wraps around what are called histone proteins, forming regularly spaced spherical bodies called nucleosomes. Thus, large portions of the genetic material are inaccessible to the gene reading machinery. Scientists at the German Cancer Research Center have now simulated at high time resolution how short DNA segments repeatedly detach spontaneously from the nucleosome. The group has been the first to demonstrate that the spool-shaped histone proteins have an active role in opening access to the genetic information.

Histones are evolutionary highly conserved proteins which are much the same in man, mouse or threadworm. They serve as coils around which the DNA molecule, a thread of several feet, wraps in the cell nucleus. Up until recent years, histones were believed to be little more than DNA packaging material. However, by now it is known that they also determine which genes are read and which are not read; thus, they actively participate in regulating many cell functions.

At DKFZ, Professor Dr. Jrg Langowski is studying the interactions of DNA and its "packaging" at a molecular level. "For DNA to be read it must be at least temporarily accessible. We wanted to find out how and, more importantly, for how long histones and DNA thread disassociate from their tightly wrapped state. This gives us a better understanding of how DNA is read and how this mechanism may possibly be disrupted in cancer cells," says Langowski, outlining the goal of his recently published research.

The packaging of DNA in the cell nucleus is extremely well studied: Each DNA spool consists of two molecules each of four different histone proteins. In each nucleosome, a DNA thread of 146 base pairs wraps around this spherical histone complex exactly 1.75 times. A small stretch of unwrapped DNA of variable length is followed by the next histone spool, forming a structure that looks like beads on a string. Prior studies have suggested that there must be a balance of "wrapped" and unwrapped DNA in the cell nucleus.

Langowski and his coworkers have now been able to resolve these interactions at a highly precise timescale using a novel computer simulation. The researchers observed two different spontaneously occurring open states of which the longer-lived one lasts one hundred thousandth of a second, while the shorter-lived one, during which exactly nine DNA building blocks dissociate from the nucleosome, lasts no more than a few millionths of a second. The group discovered that in both cases the free end of the H3 histone actively moves between protein core and DNA, thus detaching short DNA segments. The investigators assume that once the DNA segments are released from the protein binding, more segments of the DNA thread can be unwrapped more easily.

An interesting observation in this context is that the cell attaches a multitude of chemical, or what is called epigenetic, tags to exactly this free end of the H3 histone. These tags which are often altered in tumor cells have an influence on which genes are read and which are not. "Our observations now also confirm at an atomic level that the H3 tail plays a key role in determining when DNA is accessible and genes can be read and when this is not the case. It is what you could call a foot in the door to access the genetic information," said Langowski interpreting his results.


'/>"/>

Contact: Dr. Sibylle Kohlstaedt
s.kohlstaedt@dkfz.de
Helmholtz Association of German Research Centres
Source:Eurekalert

Related biology news :

1. Perception and preference may have genetic link to obesity
2. UC Santa Barbara researchers discover genetic link between visual pathways of hydras and humans
3. Will a genetic mutation cause trouble? Ask Spliceman
4. Nearby chimpanzee populations show much greater genetic diversity than distant human populations
5. Cleveland Clinic Childrens Hospital launches study to genetically test for autism
6. Genetics of endangered African monkey suggest troubles from warming climate
7. Inherited epigenetics produced record fast evolution
8. Optogenetic tool elucidated
9. Story on human genetic origins is one of EurekAlert!’s most-visited releases in 2011
10. New research shows childhood adversity causes changes in genetics
11. Genetic risk for elevated arsenic toxicity discovered
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/2/2016)... YORK , Feb. 2, 2016 /PRNewswire/ ... facilities are primarily focused on medical screening ... measure point-of-care parameters. Wearable devices that facilitate ... user,s freedom of movement are being bolstered ... for human biomedical signal acquisition coupled with ...
(Date:2/2/2016)... --Technology Enhancements Accelerate Growth of X-ray Imaging This ... computed radiography markets in Thailand , ... (TIM). It provides an in-depth analysis of ... regional market drivers and restraints. The study offers revenue ... attractiveness, both for digital and computed radiography. Market participants ...
(Date:2/1/2016)... Canada , February 1, 2016 ... technological advancements to drive global touchfree intuitive gesture control ... --> Rising sales of consumer electronics coupled ... gesture control market size through ... consumer electronics coupled with new technological advancements to drive ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... ... February 11, 2016 , ... Reichert Technologies, ... continues today to pursue the highest level of accuracy and quality with the ... Refractometer and the AR5 Refractometer. Accurate, reliable and tough enough for the ...
(Date:2/11/2016)... ... , ... Global Stem Cells Group, has announced ... new facility will provide advanced protocols and state-of-the-art techniques in cellular medicine, focusing ... The new GSCG clinic is headed by four prominent Ecuadorian physicians, including Pablo ...
(Date:2/10/2016)... 10, 2016 Early-career researchers from ... Peru , Uganda and Yemen ... health and nutrition   Indonesia , ... and Yemen are being honored for their ... are also celebrated for mentoring young women scientists who are pursuing careers ...
(Date:2/10/2016)... Feb. 10, 2016 NX Prenatal Inc., a ... NeXosome® technology for early warning of adverse pregnancy ... recent study by Dr. Thomas McElrath ... Maternal Fetal Medicine,s (SMFM) annual meeting held in ... , 2016.  The presentation reported initial positive top-line ...
Breaking Biology Technology: