Studies on substrate specificity of Jmjd2a-c histone demethylases.
Jumonji domain containing iron (II), 2-oxoglutarate (2OG)-dependent dioxygenases from Jmjd2 family demethylate trimethylated histone3-lysine 9 (H3-K9me3), and also H3-K9me2 and H3-K36me3, albeit at lower rates. Recently, we have identified the first non-histone substrates of JmjD2 demethylases. Here, we studied the substrate specificity of Jmjd2a-c demethylases using site-directed mutagenesis and novel non-histone substrates. We identified preference of Arg at -1 position and a smaller amino acid at -2 position using both singly and doubly mutated peptide substrates by Jmjd2a-c demethylases. Our results also identified similarities in substrate selectivity by H3-K9 methyltransferase, G9a and Jmjd2 demethylases despite their distinct reaction mechanisms.
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, MO 64108-2718, USA.
V K Chaithanya
VK
Ponnaluri
Divya Teja
DT
Vavilala
Mridul
M
Mukherji
D001120:Arginine / Q000737:chemistry / Q000235:genetics; D003001:Cloning, Molecular; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry* / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D013379:Substrate Specificity
C413655:KDM4C protein, human; D001120:Arginine; D056484:Jumonji Domain-Containing Histone Demethylases; C523637:KDM4B protein, human; C494424:KDM4A protein, human