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
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences