Publications

• The 2-oxoglutarate-dependent oxygenase JMJD6 catalyses oxidation of lysine residues to give 5S-hydroxylysine residues.

  Mantri M., Loik N.D., Hamed R.B., Claridge T.D., McCullagh J.S., Schofield C.J.

  Amino acid analyses reveal that JMJD6-catalysed hydroxylation of RNA-splicing regulatory protein fragments occurs to give hydroxylysine products with 5S stereochemistry. This contrasts with collagen lysyl hydroxylases, which give 5R-hydroxylated products. The work suggests that more than one subfa ... >> More

  Amino acid analyses reveal that JMJD6-catalysed hydroxylation of RNA-splicing regulatory protein fragments occurs to give hydroxylysine products with 5S stereochemistry. This contrasts with collagen lysyl hydroxylases, which give 5R-hydroxylated products. The work suggests that more than one subfamily of lysyl hydroxylases has evolved and illustrates the importance of stereochemical assignments in proteomic analyses. << Less

  Chembiochem 12:531-534(2011) [PubMed] [EuropePMC]

• JMJD6 is a histone arginine demethylase.

  Chang B., Chen Y., Zhao Y., Bruick R.K.

  Arginine methylation occurs on a number of proteins involved in a variety of cellular functions. Histone tails are known to be mono- and dimethylated on multiple arginine residues where they influence chromatin remodeling and gene expression. To date, no enzyme has been shown to reverse these regu ... >> More

  Arginine methylation occurs on a number of proteins involved in a variety of cellular functions. Histone tails are known to be mono- and dimethylated on multiple arginine residues where they influence chromatin remodeling and gene expression. To date, no enzyme has been shown to reverse these regulatory modifications. We demonstrate that the Jumonji domain-containing 6 protein (JMJD6) is a JmjC-containing iron- and 2-oxoglutarate-dependent dioxygenase that demethylates histone H3 at arginine 2 (H3R2) and histone H4 at arginine 3 (H4R3) in both biochemical and cell-based assays. These findings may help explain the many developmental defects observed in the JMJD6(-/-) knockout mice. << Less

  Science 318:444-447(2007) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.

• Structure-function relationships of human JmjC oxygenases-demethylases versus hydroxylases.

  Markolovic S., Leissing T.M., Chowdhury R., Wilkins S.E., Lu X., Schofield C.J.

  The Jumonji-C (JmjC) subfamily of 2-oxoglutarate (2OG)-dependent oxygenases are of biomedical interest because of their roles in the regulation of gene expression and protein biosynthesis. Human JmjC 2OG oxygenases catalyze oxidative modifications to give either chemically stable alcohol products, ... >> More

  The Jumonji-C (JmjC) subfamily of 2-oxoglutarate (2OG)-dependent oxygenases are of biomedical interest because of their roles in the regulation of gene expression and protein biosynthesis. Human JmjC 2OG oxygenases catalyze oxidative modifications to give either chemically stable alcohol products, or in the case of N^ɛ-methyl lysine demethylation, relatively unstable hemiaminals that fragment to give formaldehyde and the demethylated product. Recent work has yielded conflicting reports as to whether some JmjC oxygenases catalyze N-methyl group demethylation or hydroxylation reactions. We review JmjC oxygenase-catalyzed reactions within the context of structural knowledge, highlighting key differences between hydroxylases and demethylases, which have the potential to inform on the possible type(s) of reactions catalyzed by partially characterized or un-characterized JmjC oxygenases in humans and other organisms. << Less

  Curr Opin Struct Biol 41:62-72(2016) [PubMed] [EuropePMC]

• The hydroxylation activity of Jmjd6 is required for its homo-oligomerization.

  Han G., Li J., Wang Y., Li X., Mao H., Liu Y., Chen C.D.

  Jumonji C-terminal (JmjC) domain-containing proteins are protein hydroxylases and histone demethylases that control gene expression. Jumonji domain-containing protein 6 (Jmjd6) is indispensable for embryonic development and has both histone arginine demethylase and lysyl-hydroxylase activities. Th ... >> More

  Jumonji C-terminal (JmjC) domain-containing proteins are protein hydroxylases and histone demethylases that control gene expression. Jumonji domain-containing protein 6 (Jmjd6) is indispensable for embryonic development and has both histone arginine demethylase and lysyl-hydroxylase activities. The protein undergoes post-translational homo-oligomerization, but the underlying mechanism remains unknown. In this study, we examined the enzymatic activity of Jmjd6 and uncovered the mechanism underlying its homo-oligomerization. An in vitro enzymatic assay monitored by matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry indicates that Jmjd6 is unable to remove the methyl group from histone arginine residues but can hydroxylate the histone H4 tail at lysine residues in a 2-oxoglutarate (2-OG)- and Fe (II)-dependent manner. A mutational analysis reveals that the homo-oligomerization of Jmjd6 requires its enzymatic activity and the N- and C-termini. Using an in vitro enzymatic assay, we further demonstrate that Jmjd6 can hydroxylate its N-terminus but not its C-terminus. In summary, we did not detect arginine demethylase activity for Jmjd6, but we did confirm that it could catalyze the lysyl-hydroxylation of histone peptides. In addition, we demonstrated that the homo-oligomerization of Jmjd6 requires its own enzymatic activity and the N- and C-termini. We propose that Jmjd6 forms intermolecular covalent bonds between its N- and C-termini via autohydroxylation. << Less

  J. Cell. Biochem. 113:1663-1670(2012) [PubMed] [EuropePMC]