Posttranslational modifications of histone N-terminal tails impact chromatin structure and gene transcrip- tion. While the extent of histone acetylation is deter- mined by both acetyltransferases and deacetylases, it has been unclear whether histone methylation is also regulated by enzymes with opposing activities. Here, we provide evidence that LSD1 (KIAA0601), a nuclear homolog of amine oxidases, functions as a histone demethylase and transcriptional corepressor. LSD1 specifically demethylates histone H3 lysine 4, which is linked to active transcription. Lysine demeth- ylation occurs via an oxidation reaction that generates formaldehyde. Importantly, RNAi inhibition of LSD1 causes an increase in H3 lysine 4 methylation and concomitant derepression of target genes, suggesting that LSD1 represses transcription via histone demeth- ylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dy- namic regulation of histone methylation by both his- tone methylases and demethylases.
Yujiang Shi, 1 Fei Lan, 1 Caitlin Matson, 1, Peter Mulligan, 1, Johnathan R. Whetstine, 1, Philip A. Cole, 2, Robert A. Casero, 3, & and Yang Shi1, *. (2004). Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1. Cell, 119(4), 941–953. https://doi.org/10.1039/FT9949000533