In vivo epigenetic editing of Sema6a promoter reverses transcallosal dysconnectivity caused by C11orf46/Arl14ep risk gene

Cyril J. Peter; Atsushi Saito; Yuto Hasegawa; Yuya Tanaka; Mohika Nagpal; Gabriel Perez; Emily Alway; Sergio Espeso-Gil; Tariq Fayyad; Chana Ratner; Aslihan Dincer; Achla Gupta; Lakshmi Devi; John G. Pappas; François M. Lalonde; John A. Butman; Joan C. Han; Schahram Akbarian; Atsushi Kamiya

doi:10.1038/s41467-019-12013-y

Nature Communications (Sep 2019)

In vivo epigenetic editing of Sema6a promoter reverses transcallosal dysconnectivity caused by C11orf46/Arl14ep risk gene

Cyril J. Peter,
Atsushi Saito,
Yuto Hasegawa,
Yuya Tanaka,
Mohika Nagpal,
Gabriel Perez,
Emily Alway,
Sergio Espeso-Gil,
Tariq Fayyad,
Chana Ratner,
Aslihan Dincer,
Achla Gupta,
Lakshmi Devi,
John G. Pappas,
François M. Lalonde,
John A. Butman,
Joan C. Han,
Schahram Akbarian,
Atsushi Kamiya

Affiliations

Cyril J. Peter: Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai
Atsushi Saito: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
Yuto Hasegawa: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
Yuya Tanaka: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
Mohika Nagpal: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
Gabriel Perez: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
Emily Alway: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine
Sergio Espeso-Gil: Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai
Tariq Fayyad: Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai
Chana Ratner: Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai
Aslihan Dincer: Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai
Achla Gupta: Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai
Lakshmi Devi: Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai
John G. Pappas: Department of Pediatrics, New York University School of Medicine
François M. Lalonde: Human Genetics Branch, National Institute of Mental Health
John A. Butman: Diagnostic Radiology Department, The Clinical Center of the National Institutes of Health
Joan C. Han: Unit on Metabolism and Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health
Schahram Akbarian: Friedman Brain Institute and Department of Psychiatry, Icahn School of Medicine at Mount Sinai
Atsushi Kamiya: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine

DOI: https://doi.org/10.1038/s41467-019-12013-y
Journal volume & issue: Vol. 10, no. 1
pp. 1 – 14

Abstract

Read online

Although many neuropsychiatric risk genes are known to contribute to epigenetic regulation of gene expression, very little is known about specific chromatin-associated mechanisms that govern the formation and maintenance of neuronal connectivity. Here, the authors report that transcallosal connectivity is critically dependent on C11orf46/ARL14EP, a nuclear protein encoded in the chromosome 11p13 WAGR risk locus, and that RNA-guided epigenetic editing of hyperexpressed Sema6a gene promoters in C11orf46-knockdown neurons resulted in normalization of expression and rescue of transcallosal dysconnectivity via repressive chromatin remodeling.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

About the journal