Structure And Function Of Histone Demethylase

Histone methylation, which exists mainly on both arginine and lysine residues at N terminal of histone, is recognized as a strikingly important epigenetic modification linked to heterochromatin formation, X-chromosome inactivation and genomic imprinting as well as DNA damage response. Histone methylation is dynamically regulated. Hitherto, two distinct classes of lysine demethylases have been characterized:The first class is flavin adenine dinucleotide (FAD)-dependent amine oxidases, including LSD1and LSD2. The second class is the family of JmjC-domain-containing demethylases.LSD2, the only homolog of LSD1in human genome, is an H3K4mel/2specific demethylase. Based on methods of X ray crystallography, we determined the crystal structure of humen LSD2with or without its substrate histone H3. Struture of LSD2indicates comprises a novel, unpredicted zinc finger domain with two zinc atoms, a CW-type zinc finger domain with one zinc atom, a SWIRM domain and an amine oxidase domain (AO). Structure of LSD2and its substrate complex shows a binding surface on LSD2, including an essential loop(273-278), specially recognizes residues18-26of histone H3, which could increase the binding affinity between LSD2and its substrate, and correspondingly enhance the demethylase activity of LSD2. Solving of structure of LSD2with or without its substrate provides insights into the mechanism of recognizing and catalyzing H3K4by LSD2, and puts forward new recognition sites of histone modification enzymes on H3.