This entry represents a histone demethylase (LSD1) that specifically demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a co-repressor []. This enzyme acts by oxidising the substrate by FAD to generate the corresponding imine, which is subsequently hydrolysed. This enzyme demethylates both mono- and di-methylated 'Lys-4' of histone H3 and may play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3 'Lys-4' on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. It may also demethylate 'Lys-9' of histone H3, a specific tag for epigenetic transcriptional repression, thereby leading to derepression of androgen receptor target genes. This histone demethylase is a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, AOF2/LSD1, RCOR1/CoREST and PHF21A/BHC80 []. The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. In the complex, RCOR1/CoREST strongly enhances the demethylase activity and protects it from the proteasome while PHF21A/BHC80 inhibits the demethylase activity. Interacts with the androgen receptor (AR).
