9. Wang J, Hevi S, Kurash JK, Lei H, Gay F, Bajko J, Su H, Sun W, Chang H, Xu G, Gaudet F,
Li E, Chen T (2009) The lysine demethylase LSD1 (KDM1) is required for maintenance of
global DNA methylation. Nat Genet 41:125–129
10. Yang J, Huang J, Dasgupta M, Sears N, Miyagi M, Wang B, Chance MR, Chen X, Du Y,
Wang Y, An L, Wang Q, Lu T, Zhang X, Wang Z, Stark GR (2010) Reversible methylation of
promoter-bound STAT3 by histone-modifying enzymes. Proc Natl Acad Sci U S A
107:21499–21504
11. Kontaki H, Talianidis I (2010) Lysine methylation regulates E2F1-induced cell death. Mol Cell
39:152–160
12. Cho HS, Suzuki T, Dohmae N, Hayami S, Unoki M, Yoshimatsu M, Toyokawa G, Takawa M,
Chen T, Kurash JK, Field HI, Ponder BA, Nakamura Y, Hamamoto R (2011) Demethylation of
RB regulator MYPT1 by histone demethylase LSD1 promotes cell cycle progression in cancer
cells. Cancer Res 71:655–660
13. Karytinos A, Forneris F, Profumo A, Ciossani G, Battaglioli E, Binda C, Mattevi A (2009)
A novel mammalian flavin-dependent histone demethylase. J Biol Chem 284:17775–17782
14. Fang R, Barbera AJ, Xu Y, Rutenberg M, Leonor T, Bi Q, Lan F, Mei P, Yuan GC, Lian C,
Peng J, Cheng D, Sui G, Kaiser UB, Shi Y, Shi YG (2010) Human LSD2/KDM1b/AOF1
regulates gene transcription by modulating intragenic H3K4me2 methylation. Mol Cell
39:222–233
15. Yang Z, Jiang J, Stewart MD, Qi S, Yamane K, Li J, Zhang Y, Wong J (2010) AOF1 is a histone
H3K4 demethylase possessing demethylase activity-independent repression function. Cell Res
20:276–287
16. Yang Y, Yin X, Yang H, Xu Y (2015) Histone demethylase LSD2 acts as an E3 ubiquitin ligase
and inhibits cancer cell growth through promoting proteasomal degradation of OGT. Mol Cell
58:47–59
17. Yang M, Culhane JC, Szewczuk LM, Gocke CB, Brautigam CA, Tomchick DR, Machius M,
Cole PA, Yu H (2007) Structural basis of histone demethylation by LSD1 revealed by suicide
inactivation. Nat Struct Mol Biol 14:535–539
18. Baron R, Binda C, Tortorici M, McCammon JA, Mattevi A (2011) Molecular mimicry and
ligand recognition in binding and catalysis by the histone demethylase LSD1-CoREST complex. Structure 19:212–220
19. Forneris F, Binda C, Dall’Aglio A, Fraaije MW, Battaglioli E, Mattevi A (2006) A highly
specific mechanism of histone H3-K4 recognition by histone demethylase LSD1. J Biol Chem
281:35289–35295
20. Fang R, Chen F, Dong Z, Hu D, Barbera AJ, Clark EA, Fang J, Yang Y, Mei P, Rutenberg M,
Li Z, Zhang Y, Xu Y, Yang H, Wang P, Simon MD, Zhou Q, Li J, Marynick MP, Li X, Lu H,
Kaiser UB, Kingston RE, Xu Y, Shi YG (2013) LSD2/KDM1B and its cofactor NPAC/GLYR1
endow a structural and molecular model for regulation of H3K4 demethylation. Mol Cell
49:558–570
21. Chen F, Yang H, Dong Z, Fang J, Wang P, Zhu T, Gong W, Fang R, Shi YG, Li Z, Xu Y (2013)
Structural insight into substrate recognition by histone demethylase LSD2/KDM1b. Cell Res
23:306–309
22. Zhu X, Wang J, Ju BG, Rosenfeld MG (2007) Signaling and epigenetic regulation of pituitary
development. Curr Opin Cell Biol 19:605–611
23. Hirano K, Namihira M (2016) LSD1 mediates neuronal differentiation of human fetal neural
stem cells by controlling the expression of a novel target gene, HEYL. Stem Cells
34:1872–1882
24. Chen Y, Kim J, Zhang R, Yang X, Zhang Y, Fang J, Chen Z, Teng L, Chen X, Ge H, Atadja P,
Li E, Chen T, Qi W (2016) Histone demethylase LSD1 promotes adipocyte differentiation
through repressing Wnt signaling. Cell Chem Biol 23:1228–1240
25. Schulte JH, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R, Ora I, Pajtler K, KleinHitpass L, Kuhfittig-Kulle S, Metzger E, Schűle R, Eggert A, Buettner R, Kirfel J (2009)
Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma:
implications for therapy. Cancer Res 69:2065–2071
Lysine-Specific Histone Demethylases 1/2 (LSD1/2) and Their Inhibitors
215
Li E, Chen T (2009) The lysine demethylase LSD1 (KDM1) is required for maintenance of
global DNA methylation. Nat Genet 41:125–129
10. Yang J, Huang J, Dasgupta M, Sears N, Miyagi M, Wang B, Chance MR, Chen X, Du Y,
Wang Y, An L, Wang Q, Lu T, Zhang X, Wang Z, Stark GR (2010) Reversible methylation of
promoter-bound STAT3 by histone-modifying enzymes. Proc Natl Acad Sci U S A
107:21499–21504
11. Kontaki H, Talianidis I (2010) Lysine methylation regulates E2F1-induced cell death. Mol Cell
39:152–160
12. Cho HS, Suzuki T, Dohmae N, Hayami S, Unoki M, Yoshimatsu M, Toyokawa G, Takawa M,
Chen T, Kurash JK, Field HI, Ponder BA, Nakamura Y, Hamamoto R (2011) Demethylation of
RB regulator MYPT1 by histone demethylase LSD1 promotes cell cycle progression in cancer
cells. Cancer Res 71:655–660
13. Karytinos A, Forneris F, Profumo A, Ciossani G, Battaglioli E, Binda C, Mattevi A (2009)
A novel mammalian flavin-dependent histone demethylase. J Biol Chem 284:17775–17782
14. Fang R, Barbera AJ, Xu Y, Rutenberg M, Leonor T, Bi Q, Lan F, Mei P, Yuan GC, Lian C,
Peng J, Cheng D, Sui G, Kaiser UB, Shi Y, Shi YG (2010) Human LSD2/KDM1b/AOF1
regulates gene transcription by modulating intragenic H3K4me2 methylation. Mol Cell
39:222–233
15. Yang Z, Jiang J, Stewart MD, Qi S, Yamane K, Li J, Zhang Y, Wong J (2010) AOF1 is a histone
H3K4 demethylase possessing demethylase activity-independent repression function. Cell Res
20:276–287
16. Yang Y, Yin X, Yang H, Xu Y (2015) Histone demethylase LSD2 acts as an E3 ubiquitin ligase
and inhibits cancer cell growth through promoting proteasomal degradation of OGT. Mol Cell
58:47–59
17. Yang M, Culhane JC, Szewczuk LM, Gocke CB, Brautigam CA, Tomchick DR, Machius M,
Cole PA, Yu H (2007) Structural basis of histone demethylation by LSD1 revealed by suicide
inactivation. Nat Struct Mol Biol 14:535–539
18. Baron R, Binda C, Tortorici M, McCammon JA, Mattevi A (2011) Molecular mimicry and
ligand recognition in binding and catalysis by the histone demethylase LSD1-CoREST complex. Structure 19:212–220
19. Forneris F, Binda C, Dall’Aglio A, Fraaije MW, Battaglioli E, Mattevi A (2006) A highly
specific mechanism of histone H3-K4 recognition by histone demethylase LSD1. J Biol Chem
281:35289–35295
20. Fang R, Chen F, Dong Z, Hu D, Barbera AJ, Clark EA, Fang J, Yang Y, Mei P, Rutenberg M,
Li Z, Zhang Y, Xu Y, Yang H, Wang P, Simon MD, Zhou Q, Li J, Marynick MP, Li X, Lu H,
Kaiser UB, Kingston RE, Xu Y, Shi YG (2013) LSD2/KDM1B and its cofactor NPAC/GLYR1
endow a structural and molecular model for regulation of H3K4 demethylation. Mol Cell
49:558–570
21. Chen F, Yang H, Dong Z, Fang J, Wang P, Zhu T, Gong W, Fang R, Shi YG, Li Z, Xu Y (2013)
Structural insight into substrate recognition by histone demethylase LSD2/KDM1b. Cell Res
23:306–309
22. Zhu X, Wang J, Ju BG, Rosenfeld MG (2007) Signaling and epigenetic regulation of pituitary
development. Curr Opin Cell Biol 19:605–611
23. Hirano K, Namihira M (2016) LSD1 mediates neuronal differentiation of human fetal neural
stem cells by controlling the expression of a novel target gene, HEYL. Stem Cells
34:1872–1882
24. Chen Y, Kim J, Zhang R, Yang X, Zhang Y, Fang J, Chen Z, Teng L, Chen X, Ge H, Atadja P,
Li E, Chen T, Qi W (2016) Histone demethylase LSD1 promotes adipocyte differentiation
through repressing Wnt signaling. Cell Chem Biol 23:1228–1240
25. Schulte JH, Lim S, Schramm A, Friedrichs N, Koster J, Versteeg R, Ora I, Pajtler K, KleinHitpass L, Kuhfittig-Kulle S, Metzger E, Schűle R, Eggert A, Buettner R, Kirfel J (2009)
Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma:
implications for therapy. Cancer Res 69:2065–2071
Lysine-Specific Histone Demethylases 1/2 (LSD1/2) and Their Inhibitors
215