Final Activity Report Summary - ROBERT VRIES (Functional Understanding of Neuron Specific ATP-Dependent Chromatin Remodeling Complexes)
During development from a stem cell to a fully differentiated cell, a cell undergoes dramatic changes. Gene expression, responsible for the transitions, is very tightly regulated during all stages of development. An important mechanism used to regulate gene expression is by changing the structure of the chromatin switching between an active and an inactive chromatin stage. Once a set of genes is activated or inactivated, this stage can be maintained during generations of cells.
One important group of proteins involved in this epigenetic regulation of gene expression is the BAF family of proteins. The BAF complexes contain about 10 subunits including an ATPase, such as BRG1, together responsible for remodelling the chromatin. We are studying the role of the Brg1complex in the differentiation of a neural stem cell to a neuron.
Our studies showed that:
1) The complex has specific subunits for every stage of development. A switch between the different subtypes of the BAF complex is necessary for the cell to differentiate to a neuron and vice versa for maintaining a stem cell. Misexpression of any of the subunits results in failure of a cell to maintain stem cells or to differentiate.
2) One of the families of transcription factors of the complex is BAF53 of which two subunits exist. Our studies identified that BAF53b is specifically required for dendritic outgrowth. Expression of BAF53a in a BAF53b negative cell fails to restore the phenotype resulting from the BAF53b deletion.
One important group of proteins involved in this epigenetic regulation of gene expression is the BAF family of proteins. The BAF complexes contain about 10 subunits including an ATPase, such as BRG1, together responsible for remodelling the chromatin. We are studying the role of the Brg1complex in the differentiation of a neural stem cell to a neuron.
Our studies showed that:
1) The complex has specific subunits for every stage of development. A switch between the different subtypes of the BAF complex is necessary for the cell to differentiate to a neuron and vice versa for maintaining a stem cell. Misexpression of any of the subunits results in failure of a cell to maintain stem cells or to differentiate.
2) One of the families of transcription factors of the complex is BAF53 of which two subunits exist. Our studies identified that BAF53b is specifically required for dendritic outgrowth. Expression of BAF53a in a BAF53b negative cell fails to restore the phenotype resulting from the BAF53b deletion.