DNMT3B

DNA (cytosine-5)-methyltransferase 3 beta, is an enzyme that in humans in encoded by the DNMT3B gene. Mutation in this gene are associated with immunodeficiency, centromere instability and facial anomalies syndrome.

DNMT3B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3QKJ, 3FLG, 5CIU
Identifiers
Aliases	DNMT3B, ICF, ICF1, M.HsaIIIB, DNA (cytosine-5-)-methyltransferase 3 beta, DNA methyltransferase 3 beta, FSHD4
External IDs	OMIM: 602900; MGI: 1261819; HomoloGene: 56000; GeneCards: DNMT3B; OMA:DNMT3B - orthologs
Gene location (Human) Chr. Chromosome 20 (human) Band 20q11.21 Start 32,762,385 bp End 32,809,356 bp
Gene location (Mouse) Chr. Chromosome 2 (mouse) Band 2|2 H1 Start 153,491,370 bp End 153,529,650 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte hair follicle sperm embryo gonad testicle ganglionic eminence body of pancreas ventricular zone corpus epididymis Top expressed in epiblast primitive streak embryo pelvic part of vagina paramesonephric duct epithelium of vagina ejaculatory duct tail of embryo abdominal wall embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function methyltransferase activity transferase activity DNA binding transcription corepressor activity DNA-methyltransferase activity chromatin binding metal ion binding protein binding DNA (cytosine-5-)-methyltransferase activity DNA-binding transcription factor activity, RNA polymerase II-specific histone deacetylase binding Cellular component cytoplasm intracellular membrane-bounded organelle nucleoplasm nucleus Biological process response to ionizing radiation C-5 methylation of cytosine response to estradiol response to hypoxia cellular response to hyperoxia negative regulation of transcription by RNA polymerase II response to activity cellular response to dexamethasone stimulus response to vitamin A DNA methylation methylation positive regulation of gene expression negative regulation of gene expression, epigenetic positive regulation of histone H3-K4 methylation positive regulation of neuron differentiation negative regulation of histone H3-K9 methylation regulation of gene expression response to caffeine response to toxic substance response to cocaine Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1789 13436 Ensembl ENSG00000088305 ENSMUSG00000027478 UniProt Q9UBC3 O88509 RefSeq (mRNA) NM_001207055 NM_001207056 NM_006892 NM_175848 NM_175849 NM_175850 NM_001003960 NM_001003961 NM_001003963 NM_001122997 NM_001271744 NM_001271745 NM_001271746 NM_001271747 NM_010068 RefSeq (protein) NP_001193984 NP_001193985 NP_008823 NP_787044 NP_787045 NP_787046 NP_001003960 NP_001003961 NP_001003963 NP_001116469 NP_001258673 NP_001258674 NP_001258675 NP_001258676 NP_034198 Location (UCSC) Chr 20: 32.76 – 32.81 Mb Chr 2: 153.49 – 153.53 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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 DNA methyltransferase which is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes primarily to the nucleus and its expression is developmentally regulated. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined.

Clinical significance

Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome is a result of defects in lymphocyte maturation resulting from aberrant DNA methylation caused by mutations in the DNMT3B gene.

Variants of the gene can also contribute to nicotine dependency.

Interactions

DNMT3B has been shown to interact with:

• CBX5,
• DNMT1,
• DNMT3A,
• KIF4A,
• NCAPG,
• SMC2,
• SUMO1 and
• UBE2I.

Further reading

• Wijmenga C, Hansen RS, Gimelli G, Björck EJ, Davies EG, Valentine D, Belohradsky BH, van Dongen JJ, Smeets DF, van den Heuvel LP, Luyten JA, Strengman E, Weemaes C, Pearson PL (December 2000). "Genetic variation in ICF syndrome: evidence for genetic heterogeneity". Human Mutation. 16 (6): 509–17. doi:10.1002/1098-1004(200012)16:6<509::AID-HUMU8>3.0.CO;2-V. PMID 11102980. S2CID 6746943.
• Okano M, Xie S, Li E (July 1998). "Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases". Nature Genetics. 19 (3): 219–20. doi:10.1038/890. PMID 9662389. S2CID 256263.
• Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA (June 1999). "The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors". Nucleic Acids Research. 27 (11): 2291–8. doi:10.1093/nar/27.11.2291. PMC 148793. PMID 10325416.
• Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E (August 1999). "Cloning, expression and chromosome locations of the human DNMT3 gene family". Gene. 236 (1): 87–95. doi:10.1016/S0378-1119(99)00252-8. PMID 10433969.
• Okano M, Bell DW, Haber DA, Li E (October 1999). "DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development". Cell. 99 (3): 247–57. doi:10.1016/S0092-8674(00)81656-6. PMID 10555141. S2CID 15122892.
• Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, Gartler SM (December 1999). "The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome". Proceedings of the National Academy of Sciences of the United States of America. 96 (25): 14412–7. Bibcode:1999PNAS...9614412H. doi:10.1073/pnas.96.25.14412. PMC 24450. PMID 10588719.
• Xu GL, Bestor TH, Bourc'his D, Hsieh CL, Tommerup N, Bugge M, Hulten M, Qu X, Russo JJ, Viegas-Péquignot E (November 1999). "Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene". Nature. 402 (6758): 187–91. Bibcode:1999Natur.402..187X. doi:10.1038/46052. PMID 10647011. S2CID 4338524.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Fuks F, Burgers WA, Godin N, Kasai M, Kouzarides T (May 2001). "Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription". The EMBO Journal. 20 (10): 2536–44. doi:10.1093/emboj/20.10.2536. PMC 125250. PMID 11350943.
• Kang ES, Park CW, Chung JH (December 2001). "Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1". Biochemical and Biophysical Research Communications. 289 (4): 862–8. doi:10.1006/bbrc.2001.6057. PMID 11735126.
• Rhee I, Bachman KE, Park BH, Jair KW, Yen RW, Schuebel KE, Cui H, Feinberg AP, Lengauer C, Kinzler KW, Baylin SB, Vogelstein B (April 2002). "DNMT1 and DNMT3b cooperate to silence genes in human cancer cells". Nature. 416 (6880): 552–6. Bibcode:2002Natur.416..552R. doi:10.1038/416552a. PMID 11932749. S2CID 4397868.
• Hata K, Okano M, Lei H, Li E (April 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.
• Beaulieu N, Morin S, Chute IC, Robert MF, Nguyen H, MacLeod AR (August 2002). "An essential role for DNA methyltransferase DNMT3B in cancer cell survival". The Journal of Biological Chemistry. 277 (31): 28176–81. doi:10.1074/jbc.M204734200. PMID 12015329.
• Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H, Hirohashi S (July 2002). "Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis". Proceedings of the National Academy of Sciences of the United States of America. 99 (15): 10060–5. Bibcode:2002PNAS...9910060S. doi:10.1073/pnas.152121799. PMC 126624. PMID 12110732.
• Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S (August 2002). "Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases". The EMBO Journal. 21 (15): 4183–95. doi:10.1093/emboj/cdf401. PMC 126147. PMID 12145218.
• 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 Research. 30 (17): 3831–8. doi:10.1093/nar/gkf509. PMC 137431. PMID 12202768.
• Shen H, Wang L, Spitz MR, Hong WK, Mao L, Wei Q (September 2002). "A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer". Cancer Research. 62 (17): 4992–5. PMID 12208751.
• Shirohzu H, Kubota T, Kumazawa A, Sado T, Chijiwa T, Inagaki K, Suetake I, Tajima S, Wakui K, Miki Y, Hayashi M, Fukushima Y, Sasaki H (September 2002). "Three novel DNMT3B mutations in Japanese patients with ICF syndrome". American Journal of Medical Genetics. 112 (1): 31–7. doi:10.1002/ajmg.10658. PMID 12239717.

External links

• DNMT3b at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• EC 2.1.1.37