DNMT3L

Protein-coding gene in the species Homo sapiens

DNMT3L
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2PV0, 2PVC, 2QRV, 4U7P, 4U7T

Identifiers
AliasesDNMT3L, DNA methyltransferase 3 like
External IDsOMIM: 606588; MGI: 1859287; HomoloGene: 8362; GeneCards: DNMT3L; OMA:DNMT3L - orthologs
Gene location (Human)
Chromosome 21 (human)
Chr.Chromosome 21 (human)[1]
Chromosome 21 (human)
Genomic location for DNMT3L
Genomic location for DNMT3L
Band21q22.3Start44,246,339 bp[1]
End44,262,216 bp[1]
Gene location (Mouse)
Chromosome 10 (mouse)
Chr.Chromosome 10 (mouse)[2]
Chromosome 10 (mouse)
Genomic location for DNMT3L
Genomic location for DNMT3L
Band10 C1|10 39.72 cMStart77,877,781 bp[2]
End77,899,456 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • testicle

  • liver

  • right lobe of liver

  • human kidney

  • gonad

  • lymph node

  • renal cortex

  • granulocyte

  • tonsil

  • mucosa of transverse colon
Top expressed in
  • transitional epithelium of urinary bladder

  • primary oocyte

  • blastocyst

  • zygote

  • morula

  • secondary oocyte

  • Gonadal ridge

  • spermatid

  • embryo

  • embryo
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • enzyme binding
  • enzyme regulator activity
  • enzyme activator activity
  • protein binding
  • metal ion binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
Cellular component
  • cytosol
  • nucleus
  • ESC/E(Z) complex
Biological process
  • regulation of gene expression by genetic imprinting
  • DNA methylation
  • regulation of catalytic activity
  • negative regulation of transcription, DNA-templated
  • positive regulation of catalytic activity
  • male meiosis I
  • spermatogenesis
  • cell differentiation
  • DNA methylation on cytosine
  • DNA methylation involved in gamete generation
  • stem cell differentiation
  • negative regulation of DNA methylation
  • positive regulation of DNA methylation
  • regulation of transcription by RNA polymerase II
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

29947

54427

Ensembl

ENSG00000142182

ENSMUSG00000000730

UniProt

Q9UJW3

Q9CWR8

RefSeq (mRNA)

NM_013369
NM_175867

NM_001081695
NM_001284197
NM_001284198
NM_001284199
NM_001284200

NM_019448

RefSeq (protein)

NP_037501
NP_787063

NP_001075164
NP_001271126
NP_001271127
NP_001271128
NP_001271129

NP_062321

Location (UCSC)Chr 21: 44.25 – 44.26 MbChr 10: 77.88 – 77.9 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

DNA (cytosine-5)-methyltransferase 3-like is an enzyme that in humans is encoded by the DNMT3L gene.[5][6]

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.[6]

Interactions

DNMT3L has been shown to interact with HDAC1.[7][8]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000142182 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000730 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Aapola U, Kawasaki K, Scott HS, Ollila J, Vihinen M, Heino M, et al. (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.
  6. ^ a b "Entrez Gene: DNMT3L DNA (cytosine-5-)-methyltransferase 3-like".
  7. ^ 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.
  8. ^ Deplus R, Brenner C, Burgers WA, Putmans P, Kouzarides T, de Launoit Y, et al. (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.

Further reading

  • Hattori M, Fujiyama A, Taylor TD, Taylor TD, Watanabe H, Yada T, et al. (2000). "The DNA sequence of human chromosome 21". Nature. 405 (6784): 311–9. Bibcode:2000Natur.405..311H. 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. doi:10.1242/dev.129.8.1983. 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, Putmans P, Kouzarides T, De Launoit Y, 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. S2CID 27224099.
  • Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, 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. Bibcode:2002PNAS...9916899M. 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. Bibcode:2002PNAS...9916916C. doi:10.1073/pnas.262443999. PMC 139244. PMID 12481029.
  • Huntriss J, Hinkins M, Oliver B, Harris S, Beazley J, Rutherford A, 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. S2CID 39440312.
  • Suetake I, Shinozaki F, Miyagawa J, Takeshima H, Tajima S (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, Shenmen CM, Grouse LH, Schuler G, 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, Hirozane-Kishikawa T, Dricot A, Li N, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
  • Hata K, Kusumi M, Yokomine T, Li E, Sasaki H (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. S2CID 46442710.
  • Xie ZH, Huang YN, Chen ZX, Riggs AD, Ding JP, Gowher H, 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. S2CID 20182138.
  • Hu YH, Warnatz HJ, Vanhecke D, Wagner F, Fiebitz A, Thamm S, 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, Chou C, Chédin F (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, Li K, Jia D, Yang Z, et al. (2007). "DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA". Nature. 448 (7154): 714–7. Bibcode:2007Natur.448..714O. doi:10.1038/nature05987. PMC 2650820. PMID 17687327.
  • Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X (2007). "Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation". Nature. 449 (7159): 248–51. Bibcode:2007Natur.449..248J. doi:10.1038/nature06146. PMC 2712830. PMID 17713477.