Creating a neural specific chromatin landscape by npBAF and nBAF complexes

- The development of the mammalian nervous system is accompanied by sequential changes in BAF chromatin remodeling complexes.
- Recapitulating the micro-RNA/BAF chromatin remodeling complex switch is instructive for the conversion of human fibroblasts to neurons.
- Mutations in BAF subunits have genetically dominant roles in human intellectual disability and neurodegeneration.

Several features make the chromatin environment of neurons likely to be different than any other cell type. These include the fact that several hundred types of neurons exist, each requiring specialized patterns of gene expression and in turn specialized chromatin landscapes. In addition, neurons have the most stable morphology of any cell type, a unique feature essential for memory. Yet these stable morphologies must allow the emergence of new stable morphologies in response to environmental influences permitting learning to occur by altered morphology and new synapse formation. Several years ago we found that neurons have specific chromatin remodeling mechanisms not present in any other cell type that are produced by combinatorial assembly of ATP-dependent chromatin remodeling complexes. The neural specific subunits are essential for normal neural development, learning and memory. Remarkably, recreating these neural specific complexes in fibroblasts leads to their conversion to neurons. Recently, the subunits of these complexes have been found to have genetically dominant roles in several human neurologic diseases. The genetic dominance of these mutations suggests that less severe mutations will contribute to phenotypic variation in human neuronally derived traits.