Histone demethylation mediated by the nuclear amine oxidase homolog LSD1

Yujiang Shi, Fei Lan, Caitlin Matson, Peter Mulligan, Johnathan R. Whetstine, Philip A. Cole, Robert A Casero, Yang Shi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)941-953
Number of pages13
JournalCell
Volume119
Issue number7
DOIs
StatePublished - Dec 29 2004

Fingerprint

Histones
Amines
Oxidoreductases
Histone Demethylases
Methylation
Transcription
Lysine
Genes
Acetylation
Co-Repressor Proteins
Acetyltransferases
Schizosaccharomyces
Post Translational Protein Processing
RNA Interference
Formaldehyde
Chromatin
Tail
Oxidation
Enzymes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J. R., Cole, P. A., ... Shi, Y. (2004). Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell, 119(7), 941-953. https://doi.org/10.1016/j.cell.2004.12.012

Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. / Shi, Yujiang; Lan, Fei; Matson, Caitlin; Mulligan, Peter; Whetstine, Johnathan R.; Cole, Philip A.; Casero, Robert A; Shi, Yang.

In: Cell, Vol. 119, No. 7, 29.12.2004, p. 941-953.

Research output: Contribution to journalArticle

Shi, Y, Lan, F, Matson, C, Mulligan, P, Whetstine, JR, Cole, PA, Casero, RA & Shi, Y 2004, 'Histone demethylation mediated by the nuclear amine oxidase homolog LSD1', Cell, vol. 119, no. 7, pp. 941-953. https://doi.org/10.1016/j.cell.2004.12.012
Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA et al. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004 Dec 29;119(7):941-953. https://doi.org/10.1016/j.cell.2004.12.012
Shi, Yujiang ; Lan, Fei ; Matson, Caitlin ; Mulligan, Peter ; Whetstine, Johnathan R. ; Cole, Philip A. ; Casero, Robert A ; Shi, Yang. / Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. In: Cell. 2004 ; Vol. 119, No. 7. pp. 941-953.
@article{a4b4e443d22045579de0f240334e5bf4,
title = "Histone demethylation mediated by the nuclear amine oxidase homolog LSD1",
abstract = "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.",
author = "Yujiang Shi and Fei Lan and Caitlin Matson and Peter Mulligan and Whetstine, {Johnathan R.} and Cole, {Philip A.} and Casero, {Robert A} and Yang Shi",
year = "2004",
month = "12",
day = "29",
doi = "10.1016/j.cell.2004.12.012",
language = "English (US)",
volume = "119",
pages = "941--953",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=11144332565&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11144332565&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2004.12.012

DO - 10.1016/j.cell.2004.12.012

M3 - Article

C2 - 15620353

AN - SCOPUS:11144332565

VL - 119

SP - 941

EP - 953

JO - Cell

JF - Cell

SN - 0092-8674

IS - 7

ER -