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:6/21/2016)... , June 21, 2016 NuData Security announced ... new role of principal product architect and that ... director of customer development. Both will report directly ... officer. The moves reflect NuData,s strategic growth in ... to high customer demand and customer focus values. ...
(Date:6/9/2016)... June 9, 2016 Paris ... Teleste,s video security solution to ensure the safety of people ... during the major tournament Teleste, an international ... and services, announced today that its video security solution will ... to back up public safety across the country. The system ...
(Date:6/2/2016)... -- Perimeter Surveillance & Detection Systems, Biometrics ... Support & Other Service  The latest report ... analysis of the global Border Security market . ... $17.98 billion in 2016. Now: In November ... software and hardware technologies for advanced video surveillance. ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... June 23, 2016  The Prostate Cancer Foundation (PCF) is pleased ... and faster cures for prostate cancer. Members of the Class of 2016 were ... Read More About the Class of 2016 PCF Young ... ... ...
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, ... of the Supplyframe Design Lab . Located in Pasadena, Calif., the Design ... of how hardware projects are designed, built and brought to market. , The ...
(Date:6/23/2016)... 2016 Apellis Pharmaceuticals, Inc. today announced ... of its complement C3 inhibitor, APL-2. The trials ... dose studies designed to assess the safety, tolerability, ... in healthy adult volunteers. Forty subjects ... single dose (ranging from 45 to 1,440mg) or ...
(Date:6/23/2016)... YORK , June 23, 2016 ... trading session at 4,833.32, down 0.22%; the Dow Jones Industrial ... S&P 500 closed at 2,085.45, down 0.17%. Stock-Callers.com has initiated ... INFI ), Nektar Therapeutics (NASDAQ: NKTR ), ... Therapeutics Inc. (NASDAQ: BIND ). Learn more about ...
Breaking Biology Technology: