LSD1 was the first discovered histone demethylase. Using a flavin-dependent oxidative mechanism, LSD1 demethylates the N-terminal tail of histone H3 in the context of a variety of developmental processes. This functional complexity involves the association with nuclear factors and non-coding RNAs. A number of exciting studies are uncovering the bases of these specific and diverse molecular interactions, which occur both at catalytic and non-catalytic regions of the enzyme. Alternative splicing and post-translation modifications represent further layers for modulating this complex molecular network. By combining structural methods with the usage of chemically modified histones, it is becoming possible to visualize how LSD1 and associated co-repressors recognize the nucleosome. The enzyme clamps the nucleosomal particle through multivalent interactions mediated by the non-catalytic domains, which represent prospective sites for drug design.

The growing structural and functional complexity of the LSD1/KDM1A histone demethylase

MARABELLI, CHIARA;MARROCCO, BIAGINA;MATTEVI, ANDREA
2016-01-01

Abstract

LSD1 was the first discovered histone demethylase. Using a flavin-dependent oxidative mechanism, LSD1 demethylates the N-terminal tail of histone H3 in the context of a variety of developmental processes. This functional complexity involves the association with nuclear factors and non-coding RNAs. A number of exciting studies are uncovering the bases of these specific and diverse molecular interactions, which occur both at catalytic and non-catalytic regions of the enzyme. Alternative splicing and post-translation modifications represent further layers for modulating this complex molecular network. By combining structural methods with the usage of chemically modified histones, it is becoming possible to visualize how LSD1 and associated co-repressors recognize the nucleosome. The enzyme clamps the nucleosomal particle through multivalent interactions mediated by the non-catalytic domains, which represent prospective sites for drug design.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1176462
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