Packaging and unpacking of the genome

November 06, 2015

DNA represents a dynamic form of information, balancing efficient storage and access requirements. Packaging approximately 1.8m of DNA into something as small as a cell nucleus is no mean feat, but unpacking it again to access the required sections and genes? That requires organisation.

In a nutshell, this is achieved through DNA condensed and packaged as chromatin, a complex of DNA and proteins called histones, which is constantly modified as the DNA is accessed. The histone proteins need constant replacement to maintain the correct chromatin structure required for all DNA related processes in the cell.

To understand more about the importance of histone replacement, researchers at the Babraham Institute and MRC Clinical Sciences Centre used developing mouse egg cells, oocytes. Developing oocytes provide a system where the mechanics of how DNA is packaged into cells can be explored in the absence of DNA replication, as egg cells do not divide. However, their genomes are highly active as the development of the egg involves widespread turning on and off of genes and DNA modification before the mature egg cell is ready for fertilisation. The work, published in the latest issue of Molecular Cell, relied on the Institute's expertise in single cell analysis, allowing accurate mapping of the epigenetic landscape in precious cells.

The researchers deleted a histone chaperone protein - one of a group of proteins that are responsible for replacing histones in the chromatin structure - and analysed the effects on egg cell development, DNA integrity and accumulation of DNA methylation.

"Oocytes lacking the Hira histone chaperone showed severe developmental defects which often led to cell death." said Dr Gavin Kelsey, research group leader in the Institute's Epigenetics programme and author on the paper. "The whole system is disrupted, eggs accumulate DNA damage and the altered chromatin means that genes cannot be efficiently silenced or activated. But we also uncovered an intricate relationship between the different epigenetic systems operating in the oocyte, where failure to ensure normal histone levels severely compromised deposition of methylation on the underlying DNA."

The research addresses the importance of histone turnover in maintaining genomic fidelity and adds to our understanding about the mechanisms in place to protect the integrity of the genome as it is remodelled and reshaped. Studying this in the context of the developing oocytes provides new insights into our dynamic genome, unclouded by the complications of DNA replication, and also reveals how important maintaining chromatin dynamics is to the integrity of our gametes.
-end-
This work was supported by funding from the Biotechnology and Biological Research Council and Medical Research Council (MRC) to Gavin Kelsey at the Babraham Institute and the MRC and FP7 EpiGeneSys network to Petra Hajkova at the MRC Clinical Sciences Centre.

Babraham Institute

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.