Navigation Links
Biochemistry: Unspooling DNA from nucleosomal disks
Date:5/23/2013

The tight wrapping of genomic DNA around nucleosomes in the cell nucleus makes it unavailable for gene expression. A team of Ludwig-Maximilians-Universitaet (LMU) in Munich now describes a mechanism that allows chromosomal DNA to be locally displaced from nucleosomes for transcription.

In higher organisms the genomic DNA is stored in the cell nucleus, wrapped around disk-shaped particles called nucleosomes, each consisting of two pairs of four different histone proteins and accommodating two loops of DNA. Packed in this way to form chromatin, the DNA is protected, but it is inaccessible to the enzymes that mediate DNA transcription, repair and its replication. However, so-called chromatin-remodeling factors, including histone chaperones, ensure that chromatin is maintained in a dynamic state by locally modifying nucleosome structure, interacting with histone subunits and detaching stretches of the packaged DNA from the nucleosome core.

One such factor is the FACT complex which, unlike other histone chaperones, is essential for cell division and DNA repair. FACT interacts specifically with the H2A-H2B histone dimer, which forms part of the canonical nucleosomal particle. "However, until now, we had no structural insight into how these histones are recognized, and how this interaction between FACT and H2A-H2B relates to other biological functions of the FACT complex" says Professor Andreas Ladurner, who is at the LMU's Adolf Butenandt Institute. "So basically, we had no real idea what a reorganized nucleosome might look like."

FACT masks a DNA-binding site

To close this gap in our knowledge, Ladurner and his colleagues first looked at the structure of the H2A-H2B-binding domain of the FACT complex on its own. "This analysis provided some hints as to how FACT might interact with its histone partners, but not enough information to allow us to propose a molecular mechanism for the reorganization of nucleosomes," reports Maria Hondele, first author of the new study. "However, using high-resolution X-ray crystallography, we were ultimately able to determine the structure of the whole complex formed between FACT and the histone dimer."

The conformation of the complex revealed that binding of FACT blocks a site on the histone dimer that has a high affinity for DNA. This interaction releases the DNA from the nucleosome sufficiently to permit gene transcription to proceed past the nucleosome. "And in contrast to the conventional view, this mechanism works without unwrapping the DNA completely from the nucleosome," says Ladurner. Thus, the new study affords detailed insights into the mechanisms underlying the dynamic regulation of chromatin accessibility in the cell nucleus.


'/>"/>

Contact: Luise Dirscherl
dirscherl@lmu.de
49-892-180-2706
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/16/2016)... YORK , May 16, 2016   EyeLock ... solutions, today announced the opening of an IoT Center ... to strengthen and expand the development of embedded iris ... an unprecedented level of convenience and security with unmatched ... authenticate one,s identity aside from DNA. EyeLock,s platform uses ...
(Date:5/9/2016)... UAE, May 9, 2016 Elevay ... comes to expanding freedom for high net worth professionals ... in today,s globally connected world, there is still no ... could ever duplicate sealing your deal with a firm ... passports by taking advantage of citizenship via investment programs ...
(Date:4/28/2016)... and BANGALORE, India , April 28, 2016 ... a product subsidiary of Infosys (NYSE: INFY ), ... a global partnership that will provide end customers ... mobile banking and payment services.      (Logo: ... innovation area for financial services, but it also plays a ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016 /PRNewswire/ - FACIT has announced the creation ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or "the ... a portfolio of first-in-class WDR5 inhibitors for the ... WDR5 represent an exciting class of therapies, possessing ... for cancer patients. Substantial advances have been achieved ...
(Date:6/23/2016)...  The Biodesign Challenge (BDC), a university competition that ... living systems and biotechnology, announced its winning teams at ... New York City . The teams, ... at MoMA,s Celeste Bartos Theater during the daylong summit. ... curator of architecture and design, and Suzanne Lee ...
(Date:6/23/2016)... June 23, 2016 Apellis Pharmaceuticals, Inc. ... clinical trials of its complement C3 inhibitor, APL-2. ... multiple ascending dose studies designed to assess the ... subcutaneous injection in healthy adult volunteers. ... as a single dose (ranging from 45 to ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... and technical consulting, provides a free webinar on Performing Quality Investigations: ... 2016 at 12pm CT at no charge. , Incomplete investigations are still a ...
Breaking Biology Technology: