Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
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 3,100+ 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.

Related Content

New Immunoregulation and Biomarker
Clinicians at LMU have elucidated a mechanism involved in determining the lifespan of antibody-producing cells, and identified a promising new biomarker for monitoring autoimmune diseases.
Wednesday, June 17, 2015
Scientific News
The Rise of 3D Cell Culture and in vitro Model Systems for Drug Discovery and Toxicology
An overview of the current technology and the challenges and benefits over 2D cell culture models plus some of the latest advances relating to human health research.
Grant Supports Project To Develop Simple Test To Screen For Cervical Cancer
UCLA Engineering announces funding from Bill and Melinda Gates Foundation.
Injecting New Life into Old Antibiotics
A new fully synthetic way to make a class of antibiotics called macrolides from simple building blocks is set to open up a new front in the fight against antimicrobial drug resistance.
Insight into Bacterial Resilience and Antibiotic Targets
Variant of CRISPR technology paired with computerized imaging reveals essential gene networks in bacteria.
Advancing Protein Visualization
Cryo-EM methods can determine structures of small proteins bound to potential drug candidates.
Alzheimer’s Protein Serves as Natural Antibiotic
Alzheimer's-associated amyloid plaques may be part of natural process to trap microbes, findings suggest new therapeutic strategies.
Slime Mold Reveals Clues to Immune Cells’ Directional Abilities
Study from UC San Diego identifies a protein involved in the directional ability of a slime mold.
How Do You Kill A Malaria Parasite?
Drexel University scientists have discovered an unusual mechanism for how two new antimalarial drugs operate: They give the parasite’s skin a boost in cholesterol, making it unable to traverse the narrow labyrinths of the human bloodstream. The drugs also seem to trick the parasite into reproducing prematurely.
Illuminating Hidden Gene Regulators
New super-resolution technique visualizes important role of short-lived enzyme clusters.
Supressing Intenstinal Analphylaxis in Peanut Allergy
Study from National Jewish Health shows that blockade of histamine receptors suppresses intestinal anaphylaxis in peanut allergy.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
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
3,100+ 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!