Featured Research

from universities, journals, and other organizations

Programming cells: Importance of the envelope

Date:
February 1, 2013
Source:
Ludwig-Maximilians-Universitaet Muenchen (LMU)
Summary:
In a project that began with the retinal cells of nocturnal animals and has led to fundamental insights into the organization of genomic DNA, researchers show how the nuclear envelope affects nuclear architecture - and gene regulation.

In a project that began with the retinal cells of nocturnal animals and has led to fundamental insights into the organization of genomic DNA, researchers from Ludwig-Maximilians-Universitaet (LMU) in Munich show how the nuclear envelope affects nuclear architecture -- and gene regulation.

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.


Story Source:

The above story is based on materials provided by Ludwig-Maximilians-Universitaet Muenchen (LMU). Note: Materials may be edited for content and length.


Journal Reference:

  1. Irina Solovei, AudreyS. Wang, Katharina Thanisch, ChristineS. Schmidt, Stefan Krebs, Monika Zwerger, TatianaV. Cohen, Didier Devys, Roland Foisner, Leo Peichl, Harald Herrmann, Helmut Blum, Dieter Engelkamp, ColinL. Stewart, Heinrich Leonhardt, Boris Joffe. LBR and Lamin A/C Sequentially Tether Peripheral Heterochromatin and Inversely Regulate Differentiation. Cell, 2013; 152 (3): 584 DOI: 10.1016/j.cell.2013.01.009

Cite This Page:

Ludwig-Maximilians-Universitaet Muenchen (LMU). "Programming cells: Importance of the envelope." ScienceDaily. ScienceDaily, 1 February 2013. <www.sciencedaily.com/releases/2013/02/130201114110.htm>.
Ludwig-Maximilians-Universitaet Muenchen (LMU). (2013, February 1). Programming cells: Importance of the envelope. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2013/02/130201114110.htm
Ludwig-Maximilians-Universitaet Muenchen (LMU). "Programming cells: Importance of the envelope." ScienceDaily. www.sciencedaily.com/releases/2013/02/130201114110.htm (accessed September 17, 2014).

Share This



More Plants & Animals News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Some Tobacco Farmers Thrive Amid Challenges

Some Tobacco Farmers Thrive Amid Challenges

AP (Sep. 16, 2014) The South's tobacco country is surviving, and even thriving in some cases, as demand overseas keeps growers in the fields of one of America's oldest cash crops. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

AFP (Sep. 16, 2014) Scientists say a female colossal squid weighing an estimated 350 kilograms (770 lbs) and thought to be only the second intact specimen ever found was carrying eggs when discovered in the Antarctic. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com
Raw: Scientists Examine Colossal Squid

Raw: Scientists Examine Colossal Squid

AP (Sep. 16, 2014) Squid experts in New Zealand thawed and examined an unusual catch on Tuesday: a colossal squid. It was captured in Antarctica's remote Ross Sea in December last year and has been frozen for eight months. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

AFP (Sep. 16, 2014) Since the arrival of Ebola in Ivory Coast, Ivorians have been abandoning their pets, particularly monkeys, in the fear that they may transmit the virus. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

    Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins