Lysine-specific histone demethylase 2

Definition:

Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor. Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of GLYR1 to achieve such activity, they form a multifunctional enzyme complex that modifies transcribed chromatin and facilitates Pol II transcription through nucleosomes.

References:

[1]. Fei Chen, et al. Structural insight into substrate recognition by histone demethylase LSD2/KDM1b. Cell Res. 2013 Feb;23(2):306-9. [Content Brief]

[2]. Chiara Marabelli, et al. A Tail-Based Mechanism Drives Nucleosome Demethylation by the LSD2/NPAC Multimeric Complex. Cell Rep. 2019 Apr 9;27(2):387-399.e7. [Content Brief]

[3]. Rui Fang, et al. LSD2/KDM1B and its cofactor NPAC/GLYR1 endow a structural and molecular model for regulation of H3K4 demethylation. Mol Cell. 2013 Feb 7;49(3):558-70. [Content Brief]

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