Chromatin regulation plays important roles in stem cell differentiation, tissue development and tumorigenesis. Together with histone modification and DNA methylation, ATP-dependent chromatin remodeling regulates DNA accessibility to transcription factors and determines the competence of the cells to environmental signals. During vertebrate neural development, multipotent neural stem cells/progenitors have the capability to both self-renew and to generate all the neuronal and glial cell types. The transition from multipotent proliferating neural stem cells/progenitors to neurons is accompanied with permanent exit of cell cycle and formation of distinctive patterns of axons and dendrites. Coordinated changes of chromatin structures and gene activities play a key role in this transition. We are interested in the function of the chromatin regulation in neural stem cell self-renewal, differentiation, as well as post-mitotic neuronal development. The immediate focus is the prototypical SWI/SNF-like BAF (Brg/Brm associated factors) ATP-dependent chromatin remodeling complexes. Our previous studies have shown a subunit composition change of BAF complexes during neural development and that neural progenitor npBAF complexes are essential for the self-renewal and maintenance of neural stem/progenitor cells, while neuron-specific nBAF complexes are required for activity-dependent dendritic outgrowth, a unique aspect of post-mitotic neuron development. A combination of molecular biology, biochemistry and genetic approaches will be used to investigate the molecular mechanisms of chromatin regulation of gene expression essential for neural development.
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Wu, J. I., Lessard, J., Olave, I. A., Qiu, Z. Ghosh, A., Graef, I. A., and Crabtree, G. R. (2007). Regulation of dendritic development by neuron-specific chromatin remodeling complexes. Neuron 56, 94-108 (featured in Leading Edge Cell 131, 199; Research Focus in Trends in Cell Biology 18, 48-51; Featured article in Nature Neuroscience Gateway Oct. 2007).