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- W3016965293 abstract "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 ACTL6B (originally named BAF53b ). Accordingly, ACTL6B 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 ACTL6B showed corpus callosum hypoplasia, indicating a conserved role for ACTL6B in facilitating neural connectivity. Actl6b knockout mice on two genetic backgrounds exhibited ASD-related behaviors, including social and memory impairments, repetitive behaviors, and hyperactivity. Surprisingly, mutation of Actl6b relieved repression of early response genes including AP1 transcription factors ( Fos , Fosl2 , Fosb , and Junb ), increased chromatin accessibility at AP1 binding sites, and transcriptional changes in late response genes associated with early response transcription factor activity. ACTL6B loss is thus an important cause of recessive ASD, with impaired neuron-specific chromatin repression indicated as a potential mechanism." @default.
- W3016965293 created "2020-04-24" @default.
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- W3016965293 date "2020-04-20" @default.
- W3016965293 modified "2023-10-13" @default.
- W3016965293 title "Loss of the neural-specific BAF subunit ACTL6B relieves repression of early response genes and causes recessive autism" @default.
- W3016965293 cites W1579352208 @default.
- W3016965293 cites W1787127084 @default.
- W3016965293 cites W1873397816 @default.
- W3016965293 cites W1902723445 @default.
- W3016965293 cites W1917519329 @default.
- W3016965293 cites W1926834468 @default.
- W3016965293 cites W1930143582 @default.
- W3016965293 cites W1964320082 @default.
- W3016965293 cites W1976809608 @default.
- W3016965293 cites W1977666924 @default.
- W3016965293 cites W1984313344 @default.
- W3016965293 cites W1984331840 @default.
- W3016965293 cites W2001936578 @default.
- W3016965293 cites W2003653107 @default.
- W3016965293 cites W2005809131 @default.
- W3016965293 cites W2007686616 @default.
- W3016965293 cites W2010804806 @default.
- W3016965293 cites W2024465869 @default.
- W3016965293 cites W2024663595 @default.
- W3016965293 cites W2028653421 @default.
- W3016965293 cites W2031496441 @default.
- W3016965293 cites W2041221704 @default.
- W3016965293 cites W2042524484 @default.
- W3016965293 cites W2053375011 @default.
- W3016965293 cites W2056147363 @default.
- W3016965293 cites W2056549202 @default.
- W3016965293 cites W2056556069 @default.
- W3016965293 cites W2069808171 @default.
- W3016965293 cites W2070050178 @default.
- W3016965293 cites W2076450052 @default.
- W3016965293 cites W2077416773 @default.
- W3016965293 cites W2081737839 @default.
- W3016965293 cites W2087216143 @default.
- W3016965293 cites W2092343220 @default.
- W3016965293 cites W2095377293 @default.
- W3016965293 cites W2098251401 @default.
- W3016965293 cites W2099635702 @default.
- W3016965293 cites W2114139156 @default.
- W3016965293 cites W2117757143 @default.
- W3016965293 cites W2131214833 @default.
- W3016965293 cites W2131404068 @default.
- W3016965293 cites W2154486254 @default.
- W3016965293 cites W2161534011 @default.
- W3016965293 cites W2163261207 @default.
- W3016965293 cites W2163681914 @default.
- W3016965293 cites W2168950294 @default.
- W3016965293 cites W2244640471 @default.
- W3016965293 cites W2256016639 @default.
- W3016965293 cites W2308044706 @default.
- W3016965293 cites W2345356016 @default.
- W3016965293 cites W2370481231 @default.
- W3016965293 cites W2392834811 @default.
- W3016965293 cites W2396473539 @default.
- W3016965293 cites W2407074051 @default.
- W3016965293 cites W2417957465 @default.
- W3016965293 cites W2460062293 @default.
- W3016965293 cites W2460529418 @default.
- W3016965293 cites W2480659285 @default.
- W3016965293 cites W2489911374 @default.
- W3016965293 cites W2520538943 @default.
- W3016965293 cites W2557876966 @default.
- W3016965293 cites W2566164336 @default.
- W3016965293 cites W2567190685 @default.
- W3016965293 cites W2568162413 @default.