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Literature summary extracted from

  • Bao, B.; He, Y.; Tang, D.; Li, W.; Li, H.
    Inhibition of H3K27me3 histone demethylase activity prevents the proliferative regeneration of Zebrafish lateral line neuromasts (2017), Front. Mol. Neurosci., 10, 51 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.14.18.B1 medicine H3K27me3 histone demethylase activity might be a novel therapeutic target for the treatment of hearing loss Danio rerio

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.18.B1 GSK-J4 a small molecule inhibitor, specifically inhibits the H3K27 demethylase. GSK-J4 also decreases phosphorylation of ERK1/2 (p-ERK1/2) in zebrafish larvae Danio rerio

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.18.B1 histone H3 N6,N6,N6-trimethyl-L-lysine27 + 2-oxoglutarate + O2 Danio rerio
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 histone H3 N6,N6-dimethyl-L-lysine27 + succinate + formaldehyde + CO2
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 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.18.B1 Danio rerio A0A1D5NSI1
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-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.18.B1 hair cell in the zebrafish lateral line neuromasts Danio rerio
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1.14.18.B1 larva
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 Danio rerio
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1.14.18.B1 neuromast
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 Danio rerio
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Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.18.B1 histone H3 N6,N6,N6-trimethyl-L-lysine27 + 2-oxoglutarate + O2
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 Danio rerio histone H3 N6,N6-dimethyl-L-lysine27 + succinate + formaldehyde + CO2
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.14.18.B1 H3K27 demethylase
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 Danio rerio
1.14.18.B1 H3K27me3 histone demethylase
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 Danio rerio
1.14.18.B1 kdm6ba
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 Danio rerio

General Information

EC Number General Information Comment Organism
1.14.18.B1 malfunction pharmacologic inhibition of H3K27 demethylase activity decreases the number of regenerated hair cells in response to neomycin damage. Inhibition by GSK-J4 cell causes cycle arrest and induces apoptosis in the regenerating neuromasts. Inhibition of H3K27me3 histone demethylase activity dramatically suppresses cell proliferation, activates caspase-3 levels in the regenerating neuromasts of the zebrafish lateral line, and increases the expression of p21 and p27 in neuromast cells and inhibited the ERK signaling pathway, inhibition of H3K27me3 histone demethylases by GSK-J4 significantly downregulates the phosphorylation of ERK1/2 in zebrafish Danio rerio
1.14.18.B1 physiological function H3K27 demethylases are involved in a variety of biological processes, including cell differentiation, proliferation, and cell death by regulating transcriptional activity. H3K27me3 demethylation is a key epigenetic regulator in the process of hair cell regeneration in zebrafish. The MAP kinase ERK1/2 pathway is part of the mechanism triggered by H3K27me3 inhibition to impair hair cell regeneration in zebrafish lateral line neuromasts. Specific inhibitor GSK-J4 treatment has no effect on hair cell number in the absence of neomycin damage, suggesting that H3K27 histone demethylase activity is initiated during the regeneration process to help ensure that the correct number of hair cells is regenerated Danio rerio