Lysyl 5-Hydroxylation, a Novel Histone Modification, by Jumonji Domain Containing 6 (JMJD6)*

Unoki, Motoko; Masuda, Akira; Dohmae, Naoshi; Arita, Kyohei; Yoshimatsu, Masanori; Iwai, Yukiko; Fukui, Yoshihiro; Ueda, Koji; Hamamoto, Ryuji; Shirakawa, Masahiro; Sasaki, Hidetada; Nakamura, Yusuke

doi:10.1074/jbc.m112.433284

Cited by 118 publications

(113 citation statements)

References 17 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…For example, JMJD6 has been reported variously to be an arginine demethylase (10,11), a hydroxylase (12,13), a single-stranded RNA-binding protein (14), or RNA demethylase (11). Although JMJD6 has been reported to possess histone arginine demethylase activity (10,11), we and others have been unable to replicate this result (12,(14)(15)(16)(17). Thus, the identities of proteins that reverse methylation of arginine residues, either through conventional demethylation or others, have not been resolved.…”

mentioning

confidence: 59%

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7

Liu

Wang

Lee

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Two of the unsolved, important questions about epigenetics are: do histone arginine demethylases exist, and is the removal of histone tails by proteolysis a major epigenetic modification process? Here, we report that two orphan Jumonji C domain (JmjC)-containing proteins, JMJD5 and JMJD7, have divalent cationdependent protease activities that preferentially cleave the tails of histones 2, 3, or 4 containing methylated arginines. After the initial specific cleavage, JMJD5 and JMJD7, acting as aminopeptidases, progressively digest the C-terminal products. JMJD5-deficient fibroblasts exhibit dramatically increased levels of methylated arginines and histones. Furthermore, depletion of JMJD7 in breast cancer cells greatly decreases cell proliferation. The protease activities of JMJD5 and JMJD7 represent a mechanism for removal of histone tails bearing methylated arginine residues and define a potential mechanism of transcription regulation.histone tail | arginine methylation | clipping | JMJD5/7

show abstract

mentioning

confidence: 59%

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7

Liu

Wang

Lee

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Based on phylogenetic analyses, the human homologue of TgJmjC5 is jumonji domain-containing 6 (JMJD6), which is reported to have histone arginine demethylation and lysyl hydroxylation activity (53)(54)(55)(56), with potential biological functions in gene expression (53,57,58). Preliminary knockout studies in Toxoplasma suggest that the TgJmjC5 gene results in a growth defect in tachyzoites (Z. Tampaki and K. Kim, unpublished results), and an important question for the future is the precise role of TgJmjC5 in parasitic stress responses, including those affecting the ER.…”

Section: Resultsmentioning

confidence: 99%

The Unfolded Protein Response in the Protozoan Parasite Toxoplasma gondii Features Translational and Transcriptional Control

et al. 2013

View full text Add to dashboard Cite

The unfolded protein response (UPR) is an important regulatory network that responds to perturbations in protein homeostasis in the endoplasmic reticulum (ER). In mammalian cells, the UPR features translational and transcriptional mechanisms of gene expression aimed at restoring proteostatic control. A central feature of the UPR is phosphorylation of the ␣ subunit of eukaryotic initiation factor-2 (eIF2) by PERK (EIF2AK3/PEK), which reduces the influx of nascent proteins into the ER by lowering global protein synthesis, coincident with preferential translation of key transcription activators of genes that function to expand the processing capacity of this secretory organelle. Upon ER stress, the apicomplexan parasite Toxoplasma gondii is known to induce phosphorylation of Toxoplasma eIF2␣ and lower translation initiation. To characterize the nature of the ensuing UPR in this parasite, we carried out microarray analyses to measure the changes in the transcriptome and in translational control during ER stress. We determined that a collection of transcripts linked with the secretory process are induced in response to ER stress, supporting the idea that a transcriptional induction phase of the UPR occurs in Toxoplasma. Furthermore, we determined that about 500 gene transcripts showed enhanced association with translating ribosomes during ER stress. Many of these target genes are suggested to be involved in gene expression, including JmjC5, which continues to be actively translated during ER stress. This study indicates that Toxoplasma triggers a UPR during ER stress that features both translational and transcriptional regulatory mechanisms, which is likely to be important for parasite invasion and development.

show abstract

“…These results suggest that both the association of JMJD5 with HBx and the hydroxylase activity in JMJD5 are required for efficient replication of HBV. JMJD6, which has a JmjC domain structurally similar to that of JMJD5 (36,38), possesses lysyl-hydroxylase activity and catalyzes the U2 small nuclear ribonucleoprotein auxiliary factor 65-kDa subunit (U2AF65) to regulate RNA splicing (75) and hydroxylation of lysine residues in histone (76,77). Further studies are needed to identify the molecular targets of JMJD5 in hepatocytes.…”

Section: Discussionmentioning

confidence: 99%