BBB seminar: Ola Hermanson
Leave no histone unturned: Transcriptional co-repressors regulating neural stem cell state and fate
Department of Cell and Molecular Biology & Department of Neuroscience, Center of Excellence in Developmental Biology, Karolinska Institute, Stockholm, Sweden
The fundamental role for gene expression regulation during development of the nervous system is firmly established, for example by the numerous transcription factors that have been proven to be required for proper neural progenitor proliferation, lineage decision, and specification. Recently, a more complex picture has emerged as chromatin modifying events, such as histone acetylation and methylation, have been shown to be utterly important for the correct control of gene expression. In this presentation, I will give an overview of our studies on transcriptional co-regulators, regulators of histone modifications and gene expression, and discuss some implications for these factors in the control of neural progenitor state and fate.
Cortical neural stem cells (NSC) have previously been shown to adapt cell fates usually associated with neural crest in response to members of the TGFß-family. A conceptual and molecular basis for TGFß/BMP-mediated differentiation and specification in vivo and in vitro will be presented, and we have identified novel transcriptional regulators, including the transcriptional co-repressor CtBP, that are essential for this plasticity in vivo and in vitro. We have further revealed that chemical or genetic interference of a class of histone deacetylases (HDACs) induces a rapid and efficient neuronal differentiation of NSC associated with global modifications of specific lysine residues on histone H3 but not H4. We have identified several targets for HDAC repression by gene expression profiling, and demonstrate that brain-derived neurotrophic factor (BDNF) is a bona fide HDAC target that is required for the differentiation. We propose that epigenetic mechanisms, such as chromatin modifications, are essential events in neural stem cell competence and differentiation, and nervous system development.
Host: Marit Bakke, Department of Biomedicine
Prof. Ola Hermanson's research is focused on understanding gene regulatory mechanisms that govern development of neural cells and circuits in the forebrain. He and his coworkers combine the analysis of transgenic animals in vivo with neural stem cell biology in vitro. Especially, he is interested in the regulation of transcriptional coregulators by intracellular signaling pathways downstream of cytokines and growth factors and the cellular consequences of such regulation.
Ola Hermanson received his PhD at the Department of Cell Biology, Linköping University, Sweden, and continued with postdoctoral studies at the Howard Hughes Medical Institute and Department of Medicine, University of California, San Diego, La Jolla, CA, USA, in the laboratory of Michael G. Rosenfeld. In 2002 he was appointed assistant professor at the Department of Cell and Molecular Biology (CMB), Karolinska Institute, Stockholm, Sweden, and recently moved to the Department of Neuroscience at the same institute.