@article {828,
	title = {Loss of the neural-specific BAF subunit ACTL6B relieves repression of early response genes and causes recessive autism.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {117},
	year = {2020},
	month = {2020 05 05},
	pages = {10055-10066},
	abstract = {<p>Synaptic activity in neurons leads to the rapid activation of genes involved in mammalian behavior. ATP-dependent chromatin remodelers such as the BAF complex contribute to these responses and are generally thought to activate transcription. However, the mechanisms keeping such "early activation" genes silent have been a mystery. In the course of investigating Mendelian recessive autism, we identified six families with segregating loss-of-function mutations in the neuronal BAF (nBAF) subunit  (originally named ). Accordingly,  was the most significantly mutated gene in the Simons Recessive Autism Cohort. At least 14 subunits of the nBAF complex are mutated in autism, collectively making it a major contributor to autism spectrum disorder (ASD). Patient mutations destabilized ACTL6B protein in neurons and rerouted dendrites to the wrong glomerulus in the fly olfactory system. Humans and mice lacking  showed corpus callosum hypoplasia, indicating a conserved role for  in facilitating neural connectivity.  knockout mice on two genetic backgrounds exhibited ASD-related behaviors, including social and memory impairments, repetitive behaviors, and hyperactivity. Surprisingly, mutation of  relieved repression of early response genes including AP1 transcription factors (, , , and ), increased chromatin accessibility at AP1 binding sites, and transcriptional changes in late response genes associated with early response transcription factor activity.  loss is thus an important cause of recessive ASD, with impaired neuron-specific chromatin repression indicated as a potential mechanism.</p>},
	keywords = {Actins, Adenosine Triphosphate, Animals, Autism Spectrum Disorder, Behavior, Animal, Chromatin, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, Chromosome Pairing, Corpus Callosum, Dendrites, Disease Models, Animal, DNA-Binding Proteins, Gene Expression Regulation, Hippocampus, Humans, Mice, Mice, Knockout, Mutation, Neurons, Transcription Factors},
	issn = {1091-6490},
	doi = {10.1073/pnas.1908238117},
	author = {Wenderski, Wendy and Wang, Lu and Krokhotin, Andrey and Walsh, Jessica J and Li, Hongjie and Shoji, Hirotaka and Ghosh, Shereen and George, Renee D and Miller, Erik L and Elias, Laura and Gillespie, Mark A and Son, Esther Y and Staahl, Brett T and Baek, Seung Tae and Stanley, Valentina and Moncada, Cynthia and Shipony, Zohar and Linker, Sara B and Marchetto, Maria C N and Gage, Fred H and Chen, Dillon and Sultan, Tipu and Zaki, MAH S and Ranish, Jeffrey A and Miyakawa, Tsuyoshi and Luo, Liqun and Malenka, Robert C and Crabtree, Gerald R and Gleeson, Joseph G}
}
