N-lysine methyltransferase KMT5A

Definition:

Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes. Plays a negative role in TGF-beta response regulation and a positive role in cell migration.

References:

[1]. Bing Xiao, et al. Specificity and mechanism of the histone methyltransferase Pr-Set7. Genes Dev. 2005 Jun 15;19(12):1444-54. [Content Brief]

[2]. Xiaobing Shi, et al. Modulation of p53 function by SET8-mediated methylation at lysine 382. Mol Cell. 2007 Aug 17;27(4):636-46. [Content Brief]

[3]. Jean-François Couture, et al. Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase. Genes Dev. 2005 Jun 15;19(12):1455-65. [Content Brief]

[4]. Giulia Saredi, et al. H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex. Nature. 2016 Jun 30;534(7609):714-718. [Content Brief]

[5]. Eric Julien, et al. A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1. Mol Cell. 2004 Jun 18;14(6):713-25. [Content Brief]

[6]. Tarek Abbas, et al. CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration. Mol Cell. 2013 Mar 28;49(6):1147-58. [Content Brief]

[7]. Jia Fang, et al. Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr Biol. 2002 Jul 9;12(13):1086-99. [Content Brief]

[8]. Yinliang Yin, et al. SET8 recognizes the sequence RHRK20VLRDN within the N terminus of histone H4 and mono-methylates lysine 20. J Biol Chem. 2005 Aug 26;280(34):30025-31. [Content Brief]

[9]. Kenichi Nishioka, et al. PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol Cell. 2002 Jun;9(6):1201-13. [Content Brief]

[10]. Jennifer K Sims, et al. A trans-tail histone code defined by monomethylated H4 Lys-20 and H3 Lys-9 demarcates distinct regions of silent chromatin. J Biol Chem. 2006 May 5;281(18):12760-6. [Content Brief]

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