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KDM3A catalysed formation of hydroxyacetyl-lysine on histone H3K9

ABSTRACT: Histone modifications, including N-lysine acetylation and methylation, play critical roles in eukaryotic transcription. The addition of acetyl- and methyl-groups and removal of acetyl-groups involves redox neutral reactions, whereas demethylation is O2 dependent, a reaction with potential to enable O2 availability mediated regulation, as occurs for reactions catalysed by the 2-oxoglutarate dependent hypoxia-inducible factor (HIF) hydroxylases. A screen for substrates of the HIF-regulated Jumonji-C (JmjC) lysine demethylase KDM3A led to the finding that purified recombinant KDM3A catalyses oxidation of the N-acetyl group of Lys-9 of histone H3 giving an N-hydroxyacetyl-lysine residue. Studies employing a N-hydroxyacetyl-lysine selective antibody and mass spectrometry support the cellular relevance of N-hydroxyacetyl-lysine. The combined biochemical and cellular results reveal evidence for an unanticipated O2-mediated link between histone lysine N-acetylation and JmjC catalysis. Future work can explore the biological significance of N-hydroxyacetylation, including in the hypoxic response where KDM3A plays a role in regulating HIF target genes.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Simone Sidoli

LAB HEAD: Simone Sidoli

PROVIDER: PXD057969 | Pride | 2026-02-09

REPOSITORIES: Pride

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			Action	DRS
	20230822-Ronnie_batch_6_HA-NLS_KDM3A_c-term_wt_15-04-22_AND_batch_7_synthetic_H3k9acOH.raw	Raw
	20230822_Ronnie_batch_6_HA-NLS_KDM3A_c-term_wt_15-04-22.msf	Msf
	20230822_Ronnie_batch_6_HA-NLS_KDM3A_c-term_wt_15-04-22.raw	Raw
	20230822_Ronnie_batch_7_synthetic_H3k9acOH.raw	Raw
	HA-NLS_KDM3A_c-term_mut_130821.raw	Raw

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KDM3A catalysed formation of hydroxyacetyl-lysine on histone H3K9

Project description:Histone modifications, including Ne-lysine acetylation and methylation, play critical roles in eukaryotic transcription. The addition of acetyl- and methyl-groups and removal of acetyl-groups involves redox neutral reactions, whereas demethylation is O2 dependent, a reaction with potential to enable O2 availability mediated regulation, as occurs for reactions catalysed by the 2-oxoglutarate dependent hypoxia-inducible factor (HIF) hydroxylases. A screen for substrates of the HIF-regulated Jumonji-C (JmjC) lysine demethylase KDM3A led to the finding that purified recombinant KDM3A catalyses oxidation of the Ne-acetyl group of Lys-9 of histone H3 giving an Ne-hydroxyacetyl-lysine residue. Studies employing a Ne-hydroxyacetyl-lysine selective antibody and mass spectrometry support the cellular relevance of Ne-hydroxyacetyl-lysine. The combined biochemical and cellular results reveal evidence for an unanticipated O2-mediated link between histone lysine Ne-acetylation and JmjC catalysis. Future work can explore the biological significance of Ne-hydroxyacetylation, including in the hypoxic response where KDM3A plays a role in regulating HIF target genes.

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