KDM7 is a dual demethylase for histone H3 Lys 9 and Lys 27 and functions in brain development

Published in Genes & Development

Authors:
1. Yu-ichi Tsukada1,2,3,
2. Tohru Ishitani4 and
3. Keiichi I. Nakayama1,2,5

+ Author Affiliations

1.1Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan;
2.2CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan;
3.3PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan;
4.4Division of Cell Regulation Systems, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan


Abstract

Methylation of histone H3 Lys 9 and Lys 27 (H3K9 and H3K27) is associated with transcriptional silencing. Here we show that KDM7, a JmjC domain-containing protein, catalyzes demethylation of both mono- or dimethylated H3K9 and H3K27. Inhibition of KDM7 orthologs in zebrafish resulted in developmental brain defects. KDM7 interacts with the follistatin gene locus, and KDM7 depletion in mammalian neuronal cells suppressed follistatin gene transcription in association with increased levels of dimethylated H3K9 and H3K27. Our findings identify KDM7 as a dual demethylase for H3K9 and H3K27 that functions as an eraser of silencing marks on chromatin during brain development.