Lysine-specific histone demethylase 1 (LSD1) represents the first example of an identified nuclear protein with histone demethylase activity. In particular, it plays a special role in the epigenetic regulation of gene expression, as it removes methyl groups from mono- and dimethylated lysine 4 and/or lysine 9 on histone H3 (H3K4me1/2 and H3K9me1/2), behaving as a repressor or activator of gene expression, respectively. Moreover, it has been recently found to demethylate monomethylated and dimethylated lysine 20 in histone H4 and to contribute to the balance of several other methylated lysine residues in histone H3 (i.e., H3K27, H3K36, and H3K79). Furthermore, in recent years, a plethora of nonhistone proteins have been detected as targets of LSD1 activity, suggesting that this demethylase is a fundamental player in the regulation of multiple pathways triggered in several cellular processes, including cancer progression. In this review, we analyze the molecular mechanism by which LSD1 displays its dual effect on gene expression (related to the specific lysine target), placing final emphasis on the use of pharmacological inhibitors of its activity in future clinical studies to fight cancer.

LSD1: more than demethylation of histone lysine residues / Perillo, B.; Tramontano, A.; Pezone, A.; Migliaccio, A.. - In: EXPERIMENTAL AND MOLECULAR MEDICINE. - ISSN 1226-3613. - 52:12(2020), pp. 1936-1947. [10.1038/s12276-020-00542-2]

LSD1: more than demethylation of histone lysine residues

Pezone A.
;
2020

Abstract

Lysine-specific histone demethylase 1 (LSD1) represents the first example of an identified nuclear protein with histone demethylase activity. In particular, it plays a special role in the epigenetic regulation of gene expression, as it removes methyl groups from mono- and dimethylated lysine 4 and/or lysine 9 on histone H3 (H3K4me1/2 and H3K9me1/2), behaving as a repressor or activator of gene expression, respectively. Moreover, it has been recently found to demethylate monomethylated and dimethylated lysine 20 in histone H4 and to contribute to the balance of several other methylated lysine residues in histone H3 (i.e., H3K27, H3K36, and H3K79). Furthermore, in recent years, a plethora of nonhistone proteins have been detected as targets of LSD1 activity, suggesting that this demethylase is a fundamental player in the regulation of multiple pathways triggered in several cellular processes, including cancer progression. In this review, we analyze the molecular mechanism by which LSD1 displays its dual effect on gene expression (related to the specific lysine target), placing final emphasis on the use of pharmacological inhibitors of its activity in future clinical studies to fight cancer.
2020
LSD1: more than demethylation of histone lysine residues / Perillo, B.; Tramontano, A.; Pezone, A.; Migliaccio, A.. - In: EXPERIMENTAL AND MOLECULAR MEDICINE. - ISSN 1226-3613. - 52:12(2020), pp. 1936-1947. [10.1038/s12276-020-00542-2]
File in questo prodotto:
File Dimensione Formato  
LSD1- more than demethylation of histone lysine residues.pdf

accesso aperto

Tipologia: Versione Editoriale (PDF)
Licenza: Dominio pubblico
Dimensione 1.32 MB
Formato Adobe PDF
1.32 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/872478
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 109
  • ???jsp.display-item.citation.isi??? 91
social impact