The researchers found that the lamin filamentous network is an essential element in this proper positioning, the lack of which can cause specific diseases. Lamin proteins make filaments that are located mainly at the periphery of the cell nucleus, which stores and transcribes genetic material in all living matter. The lamins maintain the nuclear shape and help organize chromosomes.
Mutations in the genes that encode lamin proteins cause 14 different diseases in man, collectively termed laminopathies. These include early aging diseases and diseases that affect peripheral neurons, heart, skin, bones and muscles.
One of the muscle diseases caused by dominant mutations in the gene encoding lamin A is Emery-Dreifuss muscular dystrophy (AD-EDMD). It is characterized by weakening in certain skeletal muscles and early contractures at the neck, elbows and Achilles tendons, as well as cardiac conduction defects. How these mutations lead to the disease was largely unknown.
By manipulating the lamin gene in the worm Caenorhabditis elegans, Prof. Yosef Gruenbaum of the Hebrew University of Jerusalem and his students Anna Mattout and Erin Bank, together with Prof. Susan Gasser of the Friedrich Miescher Institute for Biomedical Research and her students Brietta Pike, Benjamin Towbin, Adriana Gonzalez and Peter Meister were able to show that lamin is necessary for the positioning of regions in the DNA that is mostly inactive (heterochromatin).
They then introduced low levels of a lamin carrying a mutation, which in humans causes AD-EDMD, into the worms and tracked their expression. In the worms expressing the mutant lamin, they detected abnormal retention of a muscle-specific gene array at the nuclear periphery. (The effect of the mutation was specific to muscle and had no effect on other cells.) The animals expressing the mutant lamin had selectively perturbed structure of body muscle and reduced muscle function, which resemble the situation in human patients.
One important conclusion of this study, which appears in the latest online edition of the journal Current Biology, is that lamin filaments help arrange silent genes at the nuclear periphery and – during normal tissue-specific activation -- allow release of the activated normal gene.
Another conclusion is that a disease-linked local mutation in lamin can impair muscle-specific reorganization of genes during tissue-specific promoter activation in a dominant manner. This dominance and the correlated muscle dysfunction typifies, for example, Emery Dreifuss Muscular Dystrophy.
For further information: Jerry Barach, Dept. of Media Relations, the Hebrew University, Tel: 02-588-2904. Orit Sulitzeanu, Hebrew University spokesperson, Tel: 054-8820016.
Jerry Barach | Hebrew University of Jerusalem
22.02.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
Separate brain systems cooperate during learning, study finds
22.02.2018 | Brown University
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
22.02.2018 | Life Sciences
22.02.2018 | Physics and Astronomy
22.02.2018 | Earth Sciences