Regulation of dendritic development by neuron-specific chromatin remodeling complexes.
The diversity of dendritic patterns is one of the fundamental characteristics of neurons and is in part regulated by transcriptional programs initiated by electrical activity. We show that dendritic outgrowth requires a family of combinatorially assembled, neuron-specific chromatin remodeling complexes (nBAF complexes) distinguished by the actin-related protein BAF53b and based on the Brg/Brm ATPases. nBAF complexes bind tightly to the Ca(2+)-responsive dendritic regulator CREST and directly regulate genes essential for dendritic outgrowth. BAF53b is not required for nBAF complex assembly or the interaction with CREST, yet is required for their recruitment to the promoters of specific target genes. The highly homologous BAF53a protein, which is a component of neural progenitor and nonneural BAF complexes, cannot replace BAF53b's role in dendritic development. Remarkably, we find that this functional specificity is conferred by the actin fold subdomain 2 of BAF53b. These studies suggest that the genes encoding the individual subunits of BAF complexes function like letters in a ten-letter word to produce biologically specific meanings (in this case dendritic outgrowth) by combinatorial assembly of their products.
Wu
Jiang I
JI
Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
Lessard
Julie
J
Olave
Ivan A
IA
Qiu
Zilong
Z
Ghosh
Anirvan
A
Graef
Isabella A
IA
Crabtree
Gerald R
GR
D000199:Actins / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D047369:Chromatin Immunoprecipitation / Q000379:methods; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D003712:Dendrites / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology*
D000199:Actins; C485486:Actl6a protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D002118:Calcium