| 背景 |
Histone lysine demethylases (KDMs) are family of enzymes which are involved in the extensive epigenetic modification in many cellular processes such as transcription regulation, chromatin remodeling, DNA proofreading and repair, cellular proliferation, embryotic development, etc. To date, two families of histone demethylases (KDMs) have been discovered; the flavin-dependent lysine specific demethylases and the JmjC-domain containing KDMs. The flavin-dependent KDM family includes LSD1 (KDM1A/AOF2) and LSD2 (KDM1B/AOF1). Structurally, LSD1 contains a coiled-coil tower domain protruding from the AO domain responsible for interaction with its co-factors, while LSD2 possesses an aminoterminal zinc finger element that is necessary for LSD2 binding to its methylated substrate. Although LSD1 and LSD2 share significant homology of amino acid sequence in the AO domain and both enzymes demethylate lysine 4 on histone 3 in a FAD-dependent manner, it is apparent that the two enzymes also have distinct functions, and therefore may act differently in regulation of gene transcription and chromatin remodeling. While LSD1 mostly binds to the promoter region of genes, LSD2 associates primarily with the body regions of actively transcribed genes. LSD2 is not only a histone demethylase but also functions as an E3 ubiquitin ligase. |
