RNA-dependent chromatin localization of KDM4D lysine demethylase promotes H3K9me3 demethylation.
The JmjC-containing lysine demethylase, KDM4D, demethylates di-and tri-methylation of histone H3 on lysine 9 (H3K9me3). How KDM4D is recruited to chromatin and recognizes its histone substrates remains unknown. Here, we show that KDM4D binds RNA independently of its demethylase activity. We mapped two non-canonical RNA binding domains: the first is within the N-terminal spanning amino acids 115 to 236, and the second is within the C-terminal spanning amino acids 348 to 523 of KDM4D. We also demonstrate that RNA interactions with KDM4D N-terminal region are critical for its association with chromatin and subsequently for demethylating H3K9me3 in cells. This study implicates, for the first time, RNA molecules in regulating the levels of H3K9 methylation by affecting KDM4D association with chromatin.
Department of Biology, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Muhammad
M
Zoabi
Department of Biology, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Prathamesh T
PT
Nadar-Ponniah
Department of Biology, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Hanan
H
Khoury-Haddad
Department of Biology, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Marko
M
Usaj
Department of Biology, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Inbal
I
Budowski-Tal
Department of Biology, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Tali
T
Haran
Department of Biology, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Arnon
A
Henn
Department of Biology, Technion - Israel Institute of Technology, Haifa 3200003, Israel.
Yael
Y
Mandel-Gutfreund
Department of Biology, Technion - Israel Institute of Technology, Haifa 3200003, Israel ayoubn@technion.ac.il.
Nabieh
N
Ayoub
D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism
D002843:Chromatin; D006657:Histones; D016601:RNA-Binding Proteins; D012313:RNA; D056484:Jumonji Domain-Containing Histone Demethylases; C521694:KDM4D protein, human; D008239:Lysine