Identification of non-histone substrates for JMJD2A-C histone demethylases.
Recent studies have shown that some Jumonji domain containing proteins demethylate tri- and dimethylated histone lysines by catalyzing a dioxygenase reaction. Here we report the substrate specificity of Jumonji domain-2 family histone demethylases (JMJD2A-C). A candidate substrate-based approach demonstrated that in addition to its known substrate, trimethylated histone H3-lysine-9, JMJD2A-C demethylate trimethylated lysine containing peptides from WIZ, CDYL1, CSB and G9a proteins, all constituents of transcription repression complexes. Our results are consistent with lax substrate specificities observed for the iron (II), 2-oxoglutarate-dependent dioxygenases, and shed new light on signaling pathways regulated by Jumonji domain-2 family histone demethylases during epigenetic transcriptional regulation.
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108-2718, USA.
V K Chaithanya
VK
Ponnaluri
Divya Teja
DT
Vavilala
Sandeep
S
Putty
William G
WG
Gutheil
Mridul
M
Mukherji
D000595:Amino Acid Sequence; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D015398:Signal Transduction; D013379:Substrate Specificity
D006657:Histones; C413655:KDM4C protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; C523637:KDM4B protein, human; C494424:KDM4A protein, human; D008239:Lysine