DNMT3L

DNA (cytosine-5-)-methyltransferase 3-like

Rendering based on PDB 2PV0.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2PV0, 2PVC, 2QRV, 4U7P, 4U7T

Identifiers

Symbols

DNMT3L ; MGC1090

External IDs

OMIM: 606588 MGI: 1859287 HomoloGene: 8362 GeneCards: DNMT3L Gene

Gene ontology
Molecular function	• protein binding • enzyme activator activity • enzyme binding • metal ion binding
Cellular component	• nucleus • cytosol
Biological process	• DNA methylation • regulation of gene expression by genetic imprinting • spermatogenesis • gene expression • DNA methylation on cytosine • regulation of gene expression, epigenetic • positive regulation of catalytic activity • negative regulation of transcription, DNA-templated
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 21:
44.25 – 44.26 Mb

Chr 10:
78.04 – 78.06 Mb

PubMed search

DNA (cytosine-5)-methyltransferase 3-like is an enzyme that in humans is encoded by the DNMT3L gene.^[1]^[2]

Function

CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a nuclear protein with similarity to DNA methyltransferases. This protein is not thought to function as a DNA methyltransferase as it does not contain the amino acid residues necessary for methyltransferase activity. However, this protein does stimulate de novo methylation by DNA cytosine methyltransferase 3 alpha and it is thought to be required for the establishment of maternal genomic imprints. This protein also mediates transcriptional repression through interaction with histone deacetylase 1. Alternative splicing results in two transcript variants. An additional splice variant has been described but its biological validity has not been determined.^[2]

Interactions

DNMT3L has been shown to interact with HDAC1.^[3]^[4]

References

↑ Aapola U, Kawasaki K, Scott HS, Ollila J, Vihinen M, Heino M, Shintani A, Kawasaki K, Minoshima S, Krohn K, Antonarakis SE, Shimizu N, Kudoh J, Peterson P (August 2000). "Isolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5-methyltransferase 3 gene family". Genomics 65 (3): 293–8. doi:10.1006/geno.2000.6168. PMID 10857753.
1 2 "Entrez Gene: DNMT3L DNA (cytosine-5-)-methyltransferase 3-like".
↑ Aapola U, Liiv I, Peterson P (2002). "Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity". Nucleic Acids Res. 30 (16): 3602–8. doi:10.1093/nar/gkf474. PMC 134241. PMID 12177302.
↑ Deplus R, Brenner C, Burgers WA, Putmans P, Kouzarides T, de Launoit Y, Fuks F (September 2002). "Dnmt3L is a transcriptional repressor that recruits histone deacetylase". Nucleic Acids Res. 30 (17): 3831–8. doi:10.1093/nar/gkf509. PMC 137431. PMID 12202768.

Hattori M, Fujiyama A, Taylor TD, et al. (2000). "The DNA sequence of human chromosome 21". Nature 405 (6784): 311–9. doi:10.1038/35012518. PMID 10830953.
Hata K, Okano M, Lei H, Li E (2002). "Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice". Development 129 (8): 1983–93. PMID 11934864.
Burgers WA, Fuks F, Kouzarides T (2002). "DNA methyltransferases get connected to chromatin". Trends Genet. 18 (6): 275–7. doi:10.1016/S0168-9525(02)02667-7. PMID 12044346.
Aapola U, Liiv I, Peterson P (2002). "Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity". Nucleic Acids Res. 30 (16): 3602–8. doi:10.1093/nar/gkf474. PMC 134241. PMID 12177302.
Deplus R, Brenner C, Burgers WA, et al. (2002). "Dnmt3L is a transcriptional repressor that recruits histone deacetylase". Nucleic Acids Res. 30 (17): 3831–8. doi:10.1093/nar/gkf509. PMC 137431. PMID 12202768.
Kierszenbaum AL (2003). "Genomic imprinting and epigenetic reprogramming: unearthing the garden of forking paths". Mol. Reprod. Dev. 63 (3): 269–72. doi:10.1002/mrd.90011. PMID 12237941.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Chedin F, Lieber MR, Hsieh CL (2003). "The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16916–21. doi:10.1073/pnas.262443999. PMC 139244. PMID 12481029.
Huntriss J, Hinkins M, Oliver B, et al. (2004). "Expression of mRNAs for DNA methyltransferases and methyl-CpG-binding proteins in the human female germ line, preimplantation embryos, and embryonic stem cells". Mol. Reprod. Dev. 67 (3): 323–36. doi:10.1002/mrd.20030. PMID 14735494.
Suetake I, Shinozaki F, Miyagawa J, et al. (2004). "DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction". J. Biol. Chem. 279 (26): 27816–23. doi:10.1074/jbc.M400181200. PMID 15105426.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
Hata K, Kusumi M, Yokomine T, et al. (2006). "Meiotic and epigenetic aberrations in Dnmt3L-deficient male germ cells". Mol. Reprod. Dev. 73 (1): 116–22. doi:10.1002/mrd.20387. PMID 16211598.
Xie ZH, Huang YN, Chen ZX, et al. (2006). "Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L". Hum. Mol. Genet. 15 (9): 1375–85. doi:10.1093/hmg/ddl059. PMID 16543361.
Yokomine T, Hata K, Tsudzuki M, Sasaki H (2006). "Evolution of the vertebrate DNMT3 gene family: a possible link between existence of DNMT3L and genomic imprinting". Cytogenet. Genome Res. 113 (1–4): 75–80. doi:10.1159/000090817. PMID 16575165.
Hu YH, Warnatz HJ, Vanhecke D, et al. (2006). "Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins". BMC Genomics 7: 155. doi:10.1186/1471-2164-7-155. PMC 1526728. PMID 16780588.
Kareta MS, Botello ZM, Ennis JJ, et al. (2006). "Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L". J. Biol. Chem. 281 (36): 25893–902. doi:10.1074/jbc.M603140200. PMID 16829525.
Ooi SK, Qiu C, Bernstein E, et al. (2007). "DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA". Nature 448 (7154): 714–7. doi:10.1038/nature05987. PMC 2650820. PMID 17687327.
Jia D, Jurkowska RZ, Zhang X, et al. (2007). "Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation". Nature 449 (7159): 248–51. doi:10.1038/nature06146. PMC 2712830. PMID 17713477.

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DNMT3L

Function

Interactions

References

Further reading