TY - JOUR
T1 - Lysyl oxidase-like 2 (LOXL2) oxidizes trimethylated lysine 4 in histone H3
AU - Herranz, Nicolás
AU - Dave, Natàlia
AU - Millanes-Romero, Alba
AU - Pascual-Reguant, Laura
AU - Morey, Lluis
AU - Díaz, Víctor M.
AU - Lórenz-Fonfría, Víctor
AU - Gutierrez-Gallego, Ricardo
AU - Jerónimo, Celia
AU - Iturbide, Ane
AU - Di Croce, Luciano
AU - García de Herreros, Antonio
AU - Peiró, Sandra
N1 - Funding Information:
We are grateful to A Riquel and R Pe?a for technical assistance, and to R Vi?as-Castells for helpful comments. We greatly thank L Espinosa for the H3 construct. We also thank E Du?ach (Universite de Nice) for advice on the reaction mechanism, E Padr?s and the Unitat de Biof?sica (UAB) for support in the infrared experiments, and J Valle and D Andreu and the UPF Peptide Facility for the synthesis of the peptides. This work was supported by FIS (PS09/00258; CP08/00223), MEC (SAF2006-00339 and SAF2010-16089), Fundaci?n Cient?fica de la Asociaci?n Espa?ola contra el C?ncer (AECC), Instituto Carlos III/FEDER (RD06/0020/0040), and Generalitat de Catalunya (2009SGR867). SP was recipient of a Miguel Servet contract (FIS), NH was supported by a predoctoral fellowship from MEC; ND was supported by AECC fellowship, and CJ was supported by EMBO and CIHR fellowships.
Publisher Copyright:
© 2016 Federation of European Biochemical Societies
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Methylation of histone H3 lysine 4 is linked to active transcription and can be removed by LSD1 or the JmjC domain-containing proteins by amino-oxidation or hydroxylation, respectively. Here we describe that its deamination can be catalyzed by lysyl oxidase-like 2 protein (LOXL2), presenting an unconventional chemical mechanism for H3K4 modification. Infrared spectroscopy and mass spectrometry analyses demonstrated that recombinant LOXL2 specifically deaminates trimethylated H3K4. Moreover, by regulating H3K4me3 deamination, LOXL2 activity is linked with the transcriptional control of the CDH1 gene. These results reveal the existence of further H3 modification as well as a novel mechanism for H3K4me3 demethylation. Database: The GEO accession number for the data referred to this paper is GSE35600.
AB - Methylation of histone H3 lysine 4 is linked to active transcription and can be removed by LSD1 or the JmjC domain-containing proteins by amino-oxidation or hydroxylation, respectively. Here we describe that its deamination can be catalyzed by lysyl oxidase-like 2 protein (LOXL2), presenting an unconventional chemical mechanism for H3K4 modification. Infrared spectroscopy and mass spectrometry analyses demonstrated that recombinant LOXL2 specifically deaminates trimethylated H3K4. Moreover, by regulating H3K4me3 deamination, LOXL2 activity is linked with the transcriptional control of the CDH1 gene. These results reveal the existence of further H3 modification as well as a novel mechanism for H3K4me3 demethylation. Database: The GEO accession number for the data referred to this paper is GSE35600.
KW - epigenetics
KW - histone modification
KW - lysyl oxidase-like 2
KW - snail1
KW - transcriptional regulation
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U2 - 10.1111/febs.13922
DO - 10.1111/febs.13922
M3 - Article
C2 - 27735137
AN - SCOPUS:84998816220
VL - 283
SP - 4263
EP - 4273
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 23
ER -