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Ankrd11 is a chromatin regulator involved in autism that is essential for neural development

journal contribution
posted on 19.10.2018, 00:00 by D Gallagher, A Voronova, MA Zander, GI Cancino, A Bramall, MP Krause, C Abad, M Tekin, Paul Neilsen, DF Callen
© 2015 Elsevier Inc. 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, andaberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation inthe 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.

Funding

Other

History

Volume

32

Issue

1

Start Page

31

End Page

42

Number of Pages

12

eISSN

1878-1551

ISSN

1534-5807

Publisher

Cell Press

Peer Reviewed

Yes

Open Access

No

Acceptance Date

20/11/2014

External Author Affiliations

Hospital for Sick Children, Toronto; University Health Network; University of Miami; Swinburne University of Technology; University of Adelaide; University of Toronto

Era Eligible

Yes

Journal

Developmental Cell