LSD1: oxidative chemistry for multifaceted functions in chromatin regulation.
Three years after its discovery, lysine-specific demethylase 1 remains at the forefront of chromatin research. Its demethylase activity on Lys4 of histone H3 supports its role in gene repression. By contrast, the biochemical mechanisms underlying lysine-specific demethylase 1 involvement in transcriptional activation are not firmly established. Structural studies highlight a specific binding site for the histone H3 N-terminal tail and a catalytic machinery that is closely related to that of other flavin-dependent amine oxidases. These insights are crucial for the development of demethylation inhibitors. Furthermore, the exploration of putative non-histone substrates and potential signaling roles of hydrogen peroxide produced by the demethylation reaction could lead to new paradigms in chromatin biology.
Forneris
Federico
F
Dipartimento di Genetica e Microbiologia, Università di Pavia, Via Ferrata 1, Pavia, Italy.
Binda
Claudia
C
Battaglioli
Elena
E
Mattevi
Andrea
A
D000818:Animals; D002384:Catalysis; D002843:Chromatin / Q000378:metabolism*; D015195:Drug Design; D005415:Flavins / Q000378:metabolism; D005786:Gene Expression Regulation; D056466:Histone Demethylases; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008954:Models, Biological; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D002843:Chromatin; D005415:Flavins; D006657:Histones; D006861:Hydrogen Peroxide; D056466:Histone Demethylases; C495195:KDM1A protein, human; D010089:Oxidoreductases, N-Demethylating; D010100:Oxygen