title: Reprogramming human fibroblasts to neurons by recapitulating an essential microRNA-chromatin switch.
abstract: The development of the vertebrate nervous system requires a switch of ATP-dependent chromatin remodeling mechanisms, which occurs by substituting subunits within these complexes near cell cycle exit. This switching involves a triple negative genetic circuitry in which REST represses miR-9 and miR-124, which in turn repress BAF53a, which in turn repress the homologous neuron-specific BAF53b. Recapitulation of this microRNA/chromatin switch in human fibroblasts converts them to neurons. The genes involved in this fate-determining chromatin switch play genetically dominant roles in several human neurologic diseases suggesting that they are rate-limiting for aspects of human neural development. We review how this switch in ATP-dependent chromatin complexes might interface with traditional ideas about neural determination and reprogramming.
authors.affiliation: Howard Hughes Medical Institute, Department of Pathology and Developmental Biology, Stanford University Medical School, Stanford, CA 94305, USA.
authors.forename: Jiong
authors.initials: J
authors.lastname: Tang
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Yoo
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Crabtree
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D065150:Cellular Reprogramming; D002843:Chromatin / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*
chemical_list: D002843:Chromatin; D035683:MicroRNAs
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