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Content archived on 2024-05-29

Functional Understanding of Neuron Specific ATP-Dependent Chromatin Remodeling Complexes

Objective

Mammalian cells contain polymorphic ATP-dependent chromatin remodeling complexes similar to the yeast SWI/SNF complex. Because these complexes contain several subunits (including actin as well as DNA binding subunits) that are not present in the yeast complex the name BAF complexes have been adopted to raise a note of caution concerning mechanistic extrapolations. Recent work in the Crabtree laboratory has indicated that during neural development a series of these BAF chromatin remodeling complexes are expressed as cells differentiate from non-committed stem cells to periventricular neural stem cells to post mitotic neurons. For example, post mitotic neurons express the neural specific BAF53b protein, an Actin Related Protein (ARP) that occupies the place of BAF53a in the ubiquitous BAF complexes. Purification of the post mitotic neural-specific complex indicates that it contains at least 2 other subunits that are present only in neurons. Immunocytochemistry indicates that periventricular neural stem cells do not express BAF53a or b, suggesting that they have a specific complex. My goal will be to precisely define the components of the complexes present at different stages of neural development using the most recent and sensitive proteomic methods. I will be using mouse model system with different neuronal specific deletions of the BAF complex subunits such as Baf 53b and BrgI which have already been made in the Crabtree lab. If I confirm the substantial preliminary data that a neural specific complex is present, I will set out to understand why neural stem cells should have such a complex and weather or not it plays a role in the genomic plasticity associated with the stem cell state.

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Topic(s)

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Call for proposal

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FP6-2002-MOBILITY-6
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Funding Scheme

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OIF - Marie Curie actions-Outgoing International Fellowships

Coordinator

KONINKLIJKE NEDERLANDSE AKADEMIEVAN WETENSCHAPPEN
EU contribution
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Address
Kloveniersburgwal 29
AMSTERDAM
Netherlands

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Total cost

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