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Ankrd11 Is a Chromatin Regulator Involved in Autism that Is Essential for Neural Development

2014; Elsevier BV; Volume: 32; Issue: 1 Linguagem: Inglês

10.1016/j.devcel.2014.11.031

1878-1551

Denis Gallagher, Anastassia Voronova, Mark Zander, Gonzalo I. Cancino, Alexa N. Bramall, Matthew P. Krause, Clemer Abad, Mustafa Tekin, Paul M. Neilsen, David F. Callen, Stephen W. Scherer, Gordon Keller, David R. Kaplan, Katherina Walz, Freda D. Miller,

Chromatin Remodeling and Cancer

Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin and colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial chromatin regulator that controls histone acetylation and gene expression during neural development, thereby providing a likely explanation for its association with cognitive dysfunction and ASD.