TY - JOUR
T1 - Histone demethylation mediated by the nuclear amine oxidase homolog LSD1
AU - Shi, Yujiang
AU - Lan, Fei
AU - Matson, Caitlin
AU - Mulligan, Peter
AU - Whetstine, Johnathan R.
AU - Cole, Philip A.
AU - Casero, Robert A.
AU - Shi, Yang
N1 - Funding Information:
We thank Grace Gill and Keith Blackwell for critical reading and helpful comments on this manuscript. We thank Rolf Sternglanz, Yi Zhang, and Steve Tronick for reagents; Chris Walsh and Tom Ellenberger for helpful discussion; and Eric Spooner, Brian Hekking, and Benedikt Kessler of the PFPC facility, Department of Pathology, Harvard Medical School for MALDI-TOF/TOF-MS and LC-MS analyses. Y.J.S. is a fellowship award recipient from the NIH (F32GM070690). J.R.W. is a fellowship award recipient from the NIH (GM70095-02). This work was supported by a grant from the NIH (GM071004) to Y.S.
PY - 2004/12/29
Y1 - 2004/12/29
N2 - Posttranslational modifications of histone N-terminal tails impact chromatin structure and gene transcription. While the extent of histone acetylation is determined 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 demethylation 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 demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.
AB - Posttranslational modifications of histone N-terminal tails impact chromatin structure and gene transcription. While the extent of histone acetylation is determined 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 demethylation 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 demethylation. The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases.
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U2 - 10.1016/j.cell.2004.12.012
DO - 10.1016/j.cell.2004.12.012
M3 - Article
C2 - 15620353
AN - SCOPUS:11144332565
SN - 0092-8674
VL - 119
SP - 941
EP - 953
JO - Cell
JF - Cell
IS - 7
ER -