Lysine-specific histone demethylase 1B (KDM1B)

Lysine-specific histone demethylase 1B (KDM1B), also known as LSD2, is a flavin-adenine dinucleotide (FAD)-dependent amine oxidase that specifically demethylates mono- and dimethylated histone H3 lysine 4 (H3K4me1/2) [UniProt Q8NB78]. Unlike its well-characterized homolog LSD1, KDM1B possesses a unique zinc-finger motif and lacks a SANT domain, allowing it to associate with the bodies of actively transcribed genes rather than promoter regions [PubMed: 21212272]. This enzyme plays a pivotal role in the regulation of genomic imprinting, particularly during oogenesis where it is essential for establishing maternal methylation marks [PubMed: 20018868]. In clinical contexts, KDM1B is frequently overexpressed in various cancers, such as breast and lung carcinoma, where it contributes to tumor progression, cell proliferation, and the epithelial-mesenchymal transition [PubMed: 25670294]. Therapeutic targeting of KDM1B focuses on small-molecule inhibitors that bind to its catalytic amine oxidase domain, often derived from tranylcypromine scaffolds, to restore normal epigenetic signaling [PubMed: 28655716]. Research into KDM1B inhibitors is ongoing, with a focus on achieving selectivity over the closely related LSD1 and monoamine oxidase enzymes to minimize side effects [PubMed: 23139101].

Other names

LSD2AOF1Amine oxidase (flavin-containing) domain-containing protein 1C6orf193KDM1B

Inhibition of the FAD-dependent amine oxidase domain to prevent the demethylation of H3K4me1 and H3K4me2, thereby modulating the epigenetic landscape and gene transcription.