Scientists of CNMPB, MPIbpc and DZNE in Göttingen describe a molecular mechanism that controls global epigenetic programs in brain development. Published in Cell Reports.
In mammals, neurogenesis is mainly restricted to development. However, certain regions of the forebrain have the capability of generating new neurons also in the adulthood. Key mechanism is the so-called epigenetics and chromatin remodeling, which controls the expression of genes and triggers the differentiation of neuronal stem cells.
Chromatin remodeling activity and functionality of BAF complexes in forebrain development. (A) The multi-subunit BAF complex alters the chromatin structure in an energy-consuming process. By local reorganization from inactive heterochromatin to the active form (euchromatin), single genes become accessible by activating or repressing transcription factors. (B) The proteins BAF155 and BAF170 serve as scaffolding subunits to maintain the stability of the entire BAF complex. The forebrain structure is not formed in deletion mutants that lack these factors. Tuoc / CNMPB
However, there is little information on how epigenetic programs and chromatin regulation exactly interact to control the fate of neural stem cells. Scientists of the Göttingen Cluster of Excellence and the DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) at the University Medical Center Göttingen (UMG), the Max Planck Institute for Biophysical Chemistry (MPIbpc) and the German Center for Neurodegenerative Diseases (DZNE) gained striking new insight into the role of the chromatin remodeling multi-subunit BAF complex in forebrain development.
The scientists, for the first time provide evidence for a molecular mechanism that involves the BAF complex to control global epigenetic programs and gene expression programs. The findings have been published recently in the Cell Reports journal.
Original publication: Narayanan R, Pirouz M, Kerimoglu C, Kiszka K, Pham L, Wagener R, Rosenbusch J, Kessel M, Fischer A, Stoykova A, Staiger JF, Tuoc T (2014) Loss of the entire multi-subunit BAF (mSWI/SNF) complexes impairs global epigenetic programs in forebrain development. CELL REPORTS, 13(9): 1842-54.
One of the major challenges in neurobiology is to understand how the fate of neural stem cells is controlled. During brain development, the BAF multi-protein complex acts as the central relay station for the activation of differentiation programs to generate neural cells from neural stem cells. Remodeling of the chromatin structure is initiated by interaction of the complex with specific genomic sequences.
Inactive, condensed heterochromatin is converted into the active loosely packed form (euchromatin), making genes accessible for activation or inactivation by transcription factors, which are involved in neuronal differentiation processes. Areas in the genome, which are subjected to chromatin remodeling, are determined by a priori chemical modification mediated by epigenetic influences.
A full understanding of how the BAF complex exactly influences the fate of neuronal stem cells has been hindered by the absence of mutant models completely lacking BAF complexes. Here the scientists have been able to create knockout mutants lacking the entire BAF complex.
The result: The subunits BAF150 und BAF170 are central key factors, acting as scaffolding proteins for the interaction with the up to 15 subunits of the functional complex. These subunits serve as regulators of stability and functionality of the BAF complex, as indicated by a massive impairment of the murine forebrain development in BAF155/BAF170 deletion mutants.
Together with a dramatic reduction in active euchromatin, the loss of functional BAF-complexes resulted in a comprehensive decrease of gene expression events. Simultaneously, the scientists observed a global increase in repressive heterochromatin marks. The authors conclude: BAF complexes rather influence repression mechanism in neuronal cells indirectly than directly activate gene expression programs.
To be able to quickly activate the differentiation to neural cells during brain development, specific genes are maintained in a certain state. This state is significantly controlled by the presence of certain epigenetic markers, which trigger or repress transcription processes. During brain development, the BAF complex interacts with theses markers to support the switch from the inactive condition to the active state and thus initiates chromatin remodeling.
Tran Tuoc, senior author of the study, is convinced: “These findings improve our understanding of the epigenetic and chromatin remodeling as regulators of neuronal stem cell-fate and developmental plasticity. They may help to design new strategies for enhancing brain repair, e.g. in neurodegenerative disorders.”
http://www.neuroanatomie.uni-goettingen.de/en/home - Homepage of the Institute of Neuroanatomy, University Medical Center Göttingen
http://www.cnmpb.de - Cluster of Excellence and DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
Dr. Heike Conrad | idw - Informationsdienst Wissenschaft
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Life Sciences
23.11.2017 | Earth Sciences
23.11.2017 | Earth Sciences