DNA (cytosine-5)-methyltransferase 3A

Definition:

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1 (By similarity). Plays a role in paternal and maternal imprinting (By similarity). Required for methylation of most imprinted loci in germ cells (By similarity). Acts as a transcriptional corepressor for ZBTB18 (By similarity). Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites (By similarity). Can actively repress transcription through the recruitment of HDAC activity (By similarity). Also has weak auto-methylation activity on Cys-710 in absence of DNA (By similarity).

References:

[1]. Emmanuelle Viré, et al. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006 Feb 16;439(7078):871-4. [Content Brief]

[2]. Mihika Pradhan, et al. CXXC domain of human DNMT1 is essential for enzymatic activity. Biochemistry. 2008 Sep 23;47(38):10000-9. [Content Brief]

[3]. Steen K T Ooi, et al. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature. 2007 Aug 9;448(7154):714-7. [Content Brief]

[4]. Ryan W Serra, et al. A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. Elife. 2014 Mar 12;3:e02313. [Content Brief]

[5]. Patricia Heyn, et al. Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions. Nat Genet. 2019 Jan;51(1):96-105. [Content Brief]

[6]. Lunching Sun, et al. DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation. Cancer Res. 2008 Apr 15;68(8):2726-35. [Content Brief]

[7]. Marlinde L van den Boogaard, et al. Mutations in DNMT3B Modify Epigenetic Repression of the D4Z4 Repeat and the Penetrance of Facioscapulohumeral Dystrophy. Am J Hum Genet. 2016 May 5;98(5):1020-1029. [Content Brief]

[8]. Sung-Hak Kim, et al. Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B to enhance DNMT3B-mediated transcriptional repression. Biochem Biophys Res Commun. 2007 Apr 6;355(2):318-23. [Content Brief]

[9]. Sung-Hak Kim, et al. DNA methyltransferase 3B acts as a co-repressor of the human polycomb protein hPc2 to repress fibroblast growth factor receptor 3 transcription. Int J Biochem Cell Biol. 2008;40(11):2462-71. [Content Brief]

[10]. Taiping Chen, et al. A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation. J Biol Chem. 2002 Oct 11;277(41):38746-54. [Content Brief]

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