Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Nuclear Envelope Affects Nuclear Architecture - and Gene Regulation

Published: Tuesday, February 05, 2013
Last Updated: Tuesday, February 05, 2013
Bookmark and Share
Project began with the retinal cells of nocturnal animals and has led to fundamental insights into the organization of genomic DNA.

The double-stranded DNA molecules that make up the genetic material are wrapped around protein complexes to form compacted “chromatin”. The active portion of the genome is less densely packed, and thus more easily accessible, than the inactive fraction, and is referred to as euchromatin. Euchromatin is typically located in the inner regions of the cell nucleus, while much of the inactive DNA in “heterochromatin” is associated with the inner face of the nuclear envelope. This type of chromatin organization is found in almost all higher organisms and may have been invented 500 million years ago.

But there is a curious exception to this generalization. In the retinal cells of nocturnal animals, the heterochromation is localized in the central area of the nucleus, as a research group led by LMU biologists Dr. Irina Solovei and Dr. Boris Joffe showed in a previous study. “This got us interested in the mechanisms that control the distribution of chromatin,” says Professor Heinrich Leonhardt of LMU’s Biozentrum. “How can the nuclear architecture in the rod cells of nocturnal animals be inverted in this way, and what determines the typical positioning of inactive chromatin on the outskirts of the nucleus in normal cells?” Leonhardt and his team have now completed an extensive study in search of the answers.

A fundamental principle unveiled

With the help of targeted genetic manipulations in the mouse, Joffe and Solovei together with their colleagues show for the first time that there are two independent mechanisms for fixing heterochromatin to the inner face of the nuclear envelope. These mechanisms make use of two different components of the inner nuclear membrane as clamps – lamin A/C, and the so-called lamin-B receptor (LBR), which itself binds to B type lamins.

Normally the two components are used sequentially for this purpose. “In the course of differentiation, there is a switch from the LBR to lamin A/C, and there is always a least one type of tether available for attachment of heterochromatin to the nuclear periphery. But if both are missing, the inactive heterochromatin recoils like a severed elastic band and collapses in the center of the nucleus,” explains Leonhardt. Moreover, the switch seems to be a fundamental principle of genome organization and cell differentiation in mammalian cells, as the researchers concluded from the study of 39 species and the analysis of diverse tissue types in nine genetic strains of mice.

Prospects for targeted therapies

Lamin proteins not only have a structural function but also have an impact on gene regulation. Thus LBR binds B type lamins and regulates stem-cell populations by promoting the expression of genes that are important for the proliferation of rapidly dividing stem cells. The lamin A/C gene on the other hand codes for a structural component of the nuclear envelope, and regulates cellular differentiation programs like e.g. the expression of muscle-specific genes in muscle cells. Mutations in this gene result in so-called laminopathies – rare genetic diseases that are associated with a broad spectrum of clinical symptoms, including muscular dystrophy and progeria, a premature aging syndrome.

Joffe and Solovei suspect that mutations in lamin A/C affect the expression of specific genes during the maturation and differentiation of cells, with deleterious results for their function and for tissue integrity. This notion could explain the highly diverse and complex symptoms seen in patients with mutations in the lamin A/C gene - and it could open routes to the design of targeted therapies for laminopathies.

The new findings thus yield fundamentally new insights into how each of the many differentiated cell types in the body arises as the result of the precisely regulated expression of a specific complement of genes appropriate to each. “In the end, we have been brought from studies of night vision and an odd quirk of nature to the discovery of a fundamental regulatory mechanism: The nuclear envelope has a major say in development, and what kind of envelope our genetic material comes in makes a great deal of difference to our fate,” Leonhardt concludes.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
AACR 2016: Cancer Immunotherapy and Beyond
At this year's meeting there was a palpable buzz around subjects ranging from microbiomics to the tumor microenvironment and cancer vaccines, big data to in vitro and in vivo modeling and drug delivery (to name just a few).
Shining A Light On Bladder Cancer
Researchers scrutinize patterns of mutations in bladder tumor genomes, gleaning insights into the roles of DNA repair and tobacco-related DNA damage.
Monovar Drills Down Into Cancer Genome
Rice, MD Anderson develop program to ID mutations in single cancer cells.
Autism, Cancer Share a Remarkable Number of Risk Genes
Researchers with the UC Davis Comprehensive Cancer Center, MIND Institute identify more than 40 common genes.
Number Of Known Genetic Risk Factors For Endometrial Cancer Doubled
An international collaboration of researchers has identified five new gene regions that increase a woman’s risk of developing endometrial cancer, one of the most common cancers to affect women, taking the number of known gene regions associated with the disease to nine.
Genetic Variant May Help Explain Why Labradors Are Prone To Obesity
A genetic variation associated with obesity and appetite in Labrador retrievers – the UK and US’s favourite dog breed – has been identified by scientists at the University of Cambridge. The finding may explain why Labrador retrievers are more likely to become obese than dogs of other breeds.
How Scientists Use DNA to Track Disease Outbreaks
They’re the top questions on everyone’s mind when a new disease outbreak happens: where did the virus come from? When did this happen? How long has it been spreading in a particular country or group of people?
Genetic Risk Factors of Disparate Diseases Share Similar Biological Underpinnings
Penn Institute for Biomedical Informatics and colleagues identify "roadmap" of disease mechanisms to identify candidate drug targets.
Stem Cells Know How to Unwind
Research led by the Babraham Institute with collaborators in the UK, Canada and Japan has revealed a new understanding of how an open genome structure supports the long-term and unrestricted developmental potential in embryonic stem cells.
Childhood Asthma Research Receives $2M
Research into the impact of a child’s upbringing and social and physical environments on the development of asthma will receive $2 million to tackle the condition that affects as many as one in three Canadians.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!