Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

DNMT3B (DNA (cytosine-5-)-methyltransferase 3 beta)

Written2012-07Riadh Ben Gacem, Olfa Ben Abdelkrim, Sonia Ziadi, Mounir Trimeche
Department of Pathology, Farhat-Hached Hospital, Sousse, Tunisia

(Note : for Links provided by Atlas : click)

Identity

Alias_namesDNA (cytosine-5-)-methyltransferase 3 beta
Other aliasICF
ICF1
M.HsaIIIB
HGNC (Hugo) DNMT3B
LocusID (NCBI) 1789
Atlas_Id 40350
Location 20q11.21  [Link to chromosome band 20q11]
Location_base_pair Starts at 31350191 and ends at 31397162 bp from pter ( according to hg19-Feb_2009)  [Mapping DNMT3B.png]
Fusion genes
(updated 2016)
DNMT3B (20q11.21) / DUSP15 (20q11.21)DNMT3B (20q11.21) / MDM4 (1q32.1)DNMT3B (20q11.21) / SYK (9q22.2)
FUK (16q22.1) / DNMT3B (20q11.21)MDM4 (1q32.1) / DNMT3B (20q11.21)
Note DNA (cytosine-5)-methyltransferase 3B (DNMT3B) is one of the three known DNA methyltransferases with catalytic activity. This enzyme is responsible for the de novo methylation of DNA, particularly during embryogenesis (Okano et al., 1999). In fact, DNMT3B adds methyl groups to CpG dinucleotides of unmethylated DNA for establishment of new methylation pattern in genomic DNA. DNMT3B level is profoundly increased in various tumor cell lines and in numerous types of human cancers, indicating that it plays an important role in tumorigenesis (Turek-Plewa and Jagodzinski, 2005).

DNA/RNA

 
  Figure 1. DNMT3B gene is located on the long arm of chromosome 20 at position 11.2 from the base pair 31350190 to base pair 31397161. It is composed of 23 exons and 22 introns.
Description DNMT3B gene is located on the long arm of chromosome 20 at position 11.2 and is composed of 23 exons and 22 introns. This gene encodes for a protein of 853 aa. DNMT3B gene is abundantly expressed in embryonic stem cells, but its expression is decreased upon their differentiation and remains low in adult somatic tissues.
Transcription Primary transcript of DNMT3B gene can be spliced five different mRNA isoforms that are DNMT3B1, DNMT3B2, DNMT3B3, DNMT3B4 and DNMT3B5.

Protein

Note DNMT3B protein is structured with N-terminal regulatory and C-terminal catalytic domains that are linked by repeated GK dipeptides (Glycine-Lysine-repeats). The N-terminal domain possesses nuclear localization signal sequence (NLS) responsible for nucleus DNMT3B localization. The N-terminal domain plays a regulatory role, and contains a proliferating cell nuclear antigen-binding domain. This N-domain also contains a cysteine rich zinc finger DNA binding motif (ATRX), a polybromo homology domain (PHD) targeting DNMT3B to the replication foci and a PWWP tetrapeptide chromatin-binding domain (Margot et al., 2000). The two halves are packed against each other to form a single structural module that exhibits a prominent positive electrostatic potential. The PWWP domain of DNMT3B alone binds DNA in vitro, probably through its basic surface, and DNMT3B binds DNA stronger than a mutant without the domain. In addition, the PWWP domain seems to target the de novo methyltransferases to chromatin. The C-terminal domain contains six conservative motifs I, IV, VI, VIII, IX and X. Motif I and X are involved in the formation of the S-adenosylomethionine binding site. Motif IV binds the substrate cytosine at the active site. Motif VI contains the glutamyl residue serving as a proton donor. Motif IX maintains the structure of the target recognition domain (TRD). Motif VIII's function is unclear (Xie et al., 1999).
The intracellular distribution of DNMT3B enzyme is rather dynamic throughout the cell cycle, indeed this enzyme is diffusely distributed throughout the nucleoplasm during most of G1, associates with subnuclear sites of DNA replication during S-phase (Leonhardt et al.,1992), and binds to chromatin, with preference to pericentric heterochromatin, during G2 and M-phases (Easwaran et al., 2005).
Description 853 amino acids; 95751 Da.
 
  Figure 2. A: The general structure of DNMT3B protein. The N-terminal domain contains a proliferating cell nuclear antigen-binding domain, a nuclear localization signal, a tetrapeptide PWWP, essential for DNMT binding to chromatin, an ATRX cysteine-rich zinc finger DNA-binding motif and a polybromo homology domain (PHD) targeting DNMT3B to the replication foci. The C-terminal catalytic domain of DNMT3B is characterized by the presence of 6 conserved amino acid motifs, namely I, IV, VI, VIII, IX and X. Motifs I and X form S-adenosylomethionine binding site, motif IV binds cytosine at the active site, motif VI possesses glutamyl residue donating protons, and motif IX maintains the structure of the target recognition domain (TRD) usually located between motifs VIII and IX, that make base-specific contacts in the major groove of DNA (Turek-Plewa and Jagodzinski, 2005). B: The results from alternative splicing of exons 10, 21 and/or 22, have reported several different transcripts of DNMT3B. These isoforms are: DNMT3B1, DNMT3B2, DNMT3B3, DNMT3B4 and DNMT3B5. DNMT3B1 and DNMT3B2, contain all the highly conserved motifs I, IV, VI, IX and X, are enzymatically active in DNA methyltransferase essays. DNMT3B3, which lacks parts of motif IX, appears to be inactive enzyme. DNMT3B4 and DNMT3B5, encode truncated proteins that lack motifs IX and X, are presumably inactive as well. The lack motifs in DNMT3B3, DNMT3B4 and DNMT3B5 are a consequence of lack 21-22, 21 or 22 exons, respectively (Xie et al., 1999; Okano et al., 1999).
Localisation Nucleus.
Function DNMT3B is expressed at very low levels in most tissues except the testis, thyroid and bone marrow (Xie et al., 1999). DNMT3B level is profoundly increased in various tumor cell lines, indicating that it plays an important role in tumorigenesis (Robertson et al., 1999; Hermann et al., 2004). DNA methylation is a covalent chemical modification, resulting in the addition of a methyl (CH3) group at the carbon 5 position of the cytosine ring. DNMT3B uses S-adenosyl-L-methionine (AdoMet) as the source of the methyl group being transferred to the DNA bases. The methyl group of S-adenosylomethionine is bound to a sulphonium atom, which thermodynamically destabilizes the molecule and makes the relatively inert methylthiol of the methionine moiety very reactive towards nucleophilic attack by nitrogen, oxygen and sulphur atoms or activated C atoms (carbanions).
DNMT3B may also interact with DNMT1 and activate HDAC1, which deacetylates histones and represses gene transcription. This indicates that DNMT3B may be involved in chromatin remodeling associated with the modulation of gene transcription. DNMT3B can also effectively methylate C to m5C post-replicatively in unmethylated DNA. During or after replication, DNA regions may bind sequence-specific proteins which block the attachment of the methyl group to CpG dinucleotide and the formation of methylation patterns unique for each tissue. The existence of DNMT3B isoforms suggests that other factors can be involved in the binding of DNMT3B to a particular DNA region. Consequences of alternative splicing on DNMT3B's ability to interact with DNMT3L. DNMT3L stimulates the catalytic activity of DNMT3A and DNMT3B methyltransferases (Suetake et al., 2004). DNMT3L binds to the carboxyl-terminal part of DNMT3B and increases the level of activity of this enzyme (Suetake et al., 2004).
Homology DNMT3B exhibit a high degree of primary structure homology with DNMT3A. Structurally, DNMT3B and DNMT3A have a similar organization, with conserved domains: the long N-terminal region contains a PWWP domain and a cysteine-rich PHD zinc finger domain and the C-terminal catalytic domain. The same NLS and ATRX sequences were also founded in the DNMT3B and DNMT3A enzymes.

Mutations

Note ICF syndrome (standing for Immunodeficiency, Centromere instability and Facial anomalies syndrome) is a rare autosomal recessive immune disorder caused by mutations of the gene DNMT3B. Therefore, the DNMT3B mutations, like A766P and R840Q, observed in patients are the likely underlying cause of their ICF phenotypes (Xie et al., 2006).
This hereditary syndrome is characterized by centromeric instability of chromosomes 1, 9, and 16 is associated with abnormal hypomethylation of CpG sites in their pericentromeric satellite regions (Hansen et al., 1999). At the molecular level, in patient DNA, sequences such as the pericentromeric classic satellite repeats of pericentromeric regions are hypomethylated, which attributes to reduced enzymatic activity of the mutant proteins (Jeanpierre et al., 1993; Gowher and Jeltsch, 2002).
Several polymorphisms were detected at the promoter region of DNMT3B gene and may influence its activity in DNA methylation and increase the susceptibility to several cancers. DNMT3B promoter polymorphisms influence on promoter hypermethylation of genes in other interacting pathways, such as cell cycle, apoptosis, or other DNA repair pathways and may increase level of DNA damage which contributes to an increased risk for cancers. For example, C>T (rs406193), -283T>C (rs121909506), -579G>T (rs2424909), -579G>T (rs2235758) and G39179T DNMT3B polymorphisms influence DNMT3B expression, thus contributing to the genetic susceptibility to different cancers (Lee et al., 2005; Fan et al., 2008; Montgomery et al., 2004; de Vogel et al., 2009; Daraei et al., 2011).
The common DNMT3B -149C>T (rs2424913) polymorphism was found to significantly increase DNTM3B promoter activity. This up-regulates the expression of the gene and may in turn lead to aberrant methylation of CpG islands in some tumor suppressor genes (Montgomery et al., 2004). It was associated with an increased risk for lung cancer (Shen et al., 2002), prostate cancer (Singal et al., 2005), and colorectal polyps, including colorectal adenomas (Jung et al., 2008), or with prognosis of head and neck cancer (Wang et al., 2004).

Implicated in

Note
  
Entity Lung cancer
Note DNMT3B may play an oncogenic role during tumorigenesis, and its genetic variants have been consistently associated with risk of several cancers. Overexpression of DNMT3B may result in promoter hypermethylation of multiple tumor suppressor genes and ultimately lead to lung tumorigenesis and poor prognosis especially among smoking patients (Lin et al., 2007; Palakurthy et al., 2009).
Polymorphisms and haplotypes of the DNMT3B gene may influence DNMT3B activity on DNA methylation, thereby modulating the susceptibility to lung cancer. The -283T>C and -579G>T polymorphisms in the DNMT3B promoter, and their haplotypes were significantly associated with the risk of adenocarcinoma of the lung (Lee et al., 2005). These mutations up-regulate DNMT3B expression, resulting in a predisposition towards aberrant de novo methylation of CpG islands in tumor suppressor genes and DNA repair genes (Lee et al., 2005; Shen et al., 2002).
  
  
Entity Breast cancer
Note DNMT3B expression levels are significantly higher in breast cancers than in normal breast tissues, suggesting a role of this enzyme in breast tumorigenesis (Fig. 3) (Girault et al., 2003; Butcher and Rodenhiser, 2007; Ben Gacem et al., 2012). DNMT3B overexpression is correlated to the epigenetic inactivation of several tumor suppressor genes and to the aggressive phenotype in breast tumors (Roll et al., 2008; Ben Gacem et al., 2012). Some polymorphisms are associated to the development of breast tumors. DNMT3B C46359T polymorphism has been correlated to women with early-onset breast cancer, bilateral breast cancer and with a family history of the disease (Montgomery et al., 2004; Wang et al., 2004).
 
Figure 3: DNMT3B overexpression in breast cancer cells as detected by immunocytochemistry (original magnification x400).
  
  
Entity Leukemia and lymphomas
Note DNMT3B is substantially overexpressed in leukemia cells than in normal bone marrow cells (Mizuno et al., 2001). DNMT3B overexpression was correlated to hypermethylation of several tumor related genes in diffuse large B-cell lymphomas and in B-cell chronic lymphocytic leukemia (Amara et al., 2010; Kn et al., 2004). In B-cell chronic lymphocytic leukemia, DNMT3B overexpression was identified as an independent prognostic factor for predicting shortened survival of patients (Amara et al., 2010).
  
  
Entity Hepatocellular carcinoma
Note DNA hypomethylation on pericentromeric satellite regions is one of the earliest events during hepatocarcinogenesis. Overexpression of DNMT3B4 isoform and elevation of the ratio of DNMT3B4 mRNA to DNMT3B3 mRNA were both significantly correlated with the degree of DNA hypomethylation on pericentromeric satellite regions in hepatocellular carcinoma (Saito et al., 2002). DNMT3B4 overexpression induces DNA demethylation on pericentromeric satellite regions even in precancerous stages and may play critical roles in the development of hepatocellular carcinoma through chromosomal instability and aberrant expression of cancer-related genes (Saito et al., 2002).
  
  
Entity Colorectal cancer
Note The levels of DNMTs mRNA/protein in colorectal carcinomas are significantly higher than in noncancerous colorectal tissues and the highest expression range was observed with DNMT3B (Eads et al., 1999; Linhart et al., 2007; Nosho et al., 2009; Huidobro et al., 2012). The CpG island methylator phenotype (CIMP) in colorectal cancer is characterized by a widespread CpG island methylation. DNMT3B contributes to CpG island methylation, which may eventually lead to the development of CIMP-high colorectal cancer (Nosho et al., 2009; Schmidt et al., 2007).
In hereditary nonpolyposis colorectal cancer, the DNMT3B gene contains a C-to-T single nucleotide polymorphism -149 bp from the transcriptional start site that may result in increased promoter activity of the gene (Shen et al., 2002). The DNA mismatch repair mutation carriers who also carried at least one T allele for the DNMT3B promoter region C-to-T polymorphism had a 2-fold higher risk for colorectal cancer by year than those who were homozygous for the wild-type DNMT3B allele (Jones et al., 2006).
  
  
Entity Facial anomalies syndrome (ICF)
Note Facial anomalies syndrome (ICF) is an autosomal recessive disease. DNMT3B gene is often the site of ICF mutations (Ehrlich et al., 2006). ICF syndrome presents with variable combined immunodeficiency, mild facial anomalies and extravagant cytogenetic abnormalities with largely affect the pericentric regions of chromosomes 1, 9 and 16. These pericentric regions contain a type of satellite DNA termed classical satellite, or satellites 2 and 3. It is normally heavily methylated, but is nearly completely unmethylated in DNA of ICF patients. In addition to classical satellite, demethylation of DNA in ICF patients is also seen at CpG islands on the inactivate X chromosome in females (Ehrlich et al., 2008).
  

Bibliography

DNA methyltransferase DNMT3b protein overexpression as a prognostic factor in patients with diffuse large B-cell lymphomas.
Amara K, Ziadi S, Hachana M, Soltani N, Korbi S, Trimeche M.
Cancer Sci. 2010 Jul;101(7):1722-30. Epub 2010 Mar 19.
PMID 20398054
 
Clinicopathologic significance of DNA methyltransferase 1, 3a, and 3b overexpression in Tunisian breast cancers.
Ben Gacem R, Hachana M, Ziadi S, Ben Abdelkarim S, Hidar S, Trimeche M.
Hum Pathol. 2012 Oct;43(10):1731-8. doi: 10.1016/j.humpath.2011.12.022. Epub 2012 Apr 18.
PMID 22520950
 
Epigenetic inactivation of BRCA1 is associated with aberrant expression of CTCF and DNA methyltransferase (DNMT3B) in some sporadic breast tumours.
Butcher DT, Rodenhiser DI.
Eur J Cancer. 2007 Jan;43(1):210-9. Epub 2006 Oct 27.
PMID 17071074
 
DNA-methyltransferase 3B 39179 G > T polymorphism and risk of sporadic colorectal cancer in a subset of Iranian population.
Daraei A, Salehi R, Mohamadhashem F.
J Res Med Sci. 2011 Jun;16(6):807-13.
PMID 22091311
 
CpG island hypermethylation in human colorectal tumors is not associated with DNA methyltransferase overexpression.
Eads CA, Danenberg KD, Kawakami K, Saltz LB, Danenberg PV, Laird PW.
Cancer Res. 1999 May 15;59(10):2302-6.
PMID 10344733
 
Cell cycle markers for live cell analyses.
Easwaran HP, Leonhardt H, Cardoso MC.
Cell Cycle. 2005 Mar;4(3):453-5. Epub 2005 Mar 7.
PMID 15701967
 
Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF).
Ehrlich M, Jackson K, Weemaes C.
Orphanet J Rare Dis. 2006 Mar 1;1:2.
PMID 16722602
 
ICF, an immunodeficiency syndrome: DNA methyltransferase 3B involvement, chromosome anomalies, and gene dysregulation.
Ehrlich M, Sanchez C, Shao C, Nishiyama R, Kehrl J, Kuick R, Kubota T, Hanash SM.
Autoimmunity. 2008 May;41(4):253-71.
PMID 18432406
 
Promoter polymorphisms of DNMT3B and the risk of colorectal cancer in Chinese: a case-control study.
Fan H, Zhang F, Hu J, Liu D, Zhao Z.
J Exp Clin Cancer Res. 2008 Jul 28;27:24.
PMID 18662374
 
Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas.
Girault I, Tozlu S, Lidereau R, Bieche I.
Clin Cancer Res. 2003 Oct 1;9(12):4415-22.
PMID 14555514
 
Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases.
Gowher H, Jeltsch A.
J Biol Chem. 2002 Jun 7;277(23):20409-14. Epub 2002 Mar 27.
PMID 11919202
 
The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome.
Hansen RS, Wijmenga C, Luo P, Stanek AM, Canfield TK, Weemaes CM, Gartler SM.
Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14412-7.
PMID 10588719
 
Biochemistry and biology of mammalian DNA methyltransferases.
Hermann A, Gowher H, Jeltsch A.
Cell Mol Life Sci. 2004 Oct;61(19-20):2571-87.
PMID 15526163
 
A DNA methylation signature associated with aberrant promoter DNA hypermethylation of DNMT3B in human colorectal cancer.
Huidobro C, Urdinguio RG, Rodriguez RM, Mangas C, Calvanese V, Martinez-Camblor P, Ferrero C, Parra-Blanco A, Rodrigo L, Obaya AJ, Suarez-Fernandez L, Astudillo A, Hernando H, Ballestar E, Fernandez AF, Fraga MF.
Eur J Cancer. 2012 Sep;48(14):2270-81. doi: 10.1016/j.ejca.2011.12.019. Epub 2012 Jan 13.
PMID 22244828
 
An embryonic-like methylation pattern of classical satellite DNA is observed in ICF syndrome.
Jeanpierre M, Turleau C, Aurias A, Prieur M, Ledeist F, Fischer A, Viegas-Pequignot E.
Hum Mol Genet. 1993 Jun;2(6):731-5.
PMID 8102570
 
DNMT3b polymorphism and hereditary nonpolyposis colorectal cancer age of onset.
Jones JS, Amos CI, Pande M, Gu X, Chen J, Campos IM, Wei Q, Rodriguez-Bigas M, Lynch PM, Frazier ML.
Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):886-91.
PMID 16702365
 
DNA methyltransferase and alcohol dehydrogenase: gene-nutrient interactions in relation to risk of colorectal polyps.
Jung AY, Poole EM, Bigler J, Whitton J, Potter JD, Ulrich CM.
Cancer Epidemiol Biomarkers Prev. 2008 Feb;17(2):330-8.
PMID 18268116
 
Expression analysis of the epigenetic methyltransferases and methyl-CpG binding protein families in the normal B-cell and B-cell chronic lymphocytic leukemia (CLL).
Kn H, Bassal S, Tikellis C, El-Osta A.
Cancer Biol Ther. 2004 Oct;3(10):989-94. Epub 2004 Oct 2.
PMID 15467427
 
DNMT3B polymorphisms and risk of primary lung cancer.
Lee SJ, Jeon HS, Jang JS, Park SH, Lee GY, Lee BH, Kim CH, Kang YM, Lee WK, Kam S, Park RW, Kim IS, Cho YL, Jung TH, Park JY.
Carcinogenesis. 2005 Feb;26(2):403-9. Epub 2004 Nov 4.
PMID 15528220
 
A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei.
Leonhardt H, Page AW, Weier HU, Bestor TH.
Cell. 1992 Nov 27;71(5):865-73.
PMID 1423634
 
Alteration of DNA methyltransferases contributes to 5'CpG methylation and poor prognosis in lung cancer.
Lin RK, Hsu HS, Chang JW, Chen CY, Chen JT, Wang YC.
Lung Cancer. 2007 Feb;55(2):205-13. Epub 2006 Nov 30.
PMID 17140695
 
Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing.
Linhart HG, Lin H, Yamada Y, Moran E, Steine EJ, Gokhale S, Lo G, Cantu E, Ehrich M, He T, Meissner A, Jaenisch R.
Genes Dev. 2007 Dec 1;21(23):3110-22.
PMID 18056424
 
Structure and function of the mouse DNA methyltransferase gene: Dnmt1 shows a tripartite structure.
Margot JB, Aguirre-Arteta AM, Di Giacco BV, Pradhan S, Roberts RJ, Cardoso MC, Leonhardt H.
J Mol Biol. 2000 Mar 24;297(2):293-300.
PMID 10715201
 
Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia.
Mizuno S, Chijiwa T, Okamura T, Akashi K, Fukumaki Y, Niho Y, Sasaki H.
Blood. 2001 Mar 1;97(5):1172-9.
PMID 11222358
 
The DNMT3B C-->T promoter polymorphism and risk of breast cancer in a British population: a case-control study.
Montgomery KG, Liu MC, Eccles DM, Campbell IG.
Breast Cancer Res. 2004;6(4):R390-4. Epub 2004 May 19.
PMID 15217506
 
DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.
Okano M, Bell DW, Haber DA, Li E.
Cell. 1999 Oct 29;99(3):247-57.
PMID 10555141
 
Epigenetic silencing of the RASSF1A tumor suppressor gene through HOXB3-mediated induction of DNMT3B expression.
Palakurthy RK, Wajapeyee N, Santra MK, Gazin C, Lin L, Gobeil S, Green MR.
Mol Cell. 2009 Oct 23;36(2):219-30.
PMID 19854132
 
The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors.
Robertson KD, Uzvolgyi E, Liang G, Talmadge C, Sumegi J, Gonzales FA, Jones PA.
Nucleic Acids Res. 1999 Jun 1;27(11):2291-8.
PMID 10325416
 
DNMT3b overexpression contributes to a hypermethylator phenotype in human breast cancer cell lines.
Roll JD, Rivenbark AG, Jones WD, Coleman WB.
Mol Cancer. 2008 Jan 25;7:15.
PMID 18221536
 
Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis.
Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H, Hirohashi S.
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10060-5. Epub 2002 Jul 10.
PMID 12110732
 
Progressive up-regulation of genes encoding DNA methyltransferases in the colorectal adenoma-carcinoma sequence.
Schmidt WM, Sedivy R, Forstner B, Steger GG, Zochbauer-Muller S, Mader RM.
Mol Carcinog. 2007 Sep;46(9):766-72.
PMID 17538945
 
A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer.
Shen H, Wang L, Spitz MR, Hong WK, Mao L, Wei Q.
Cancer Res. 2002 Sep 1;62(17):4992-5.
PMID 12208751
 
Polymorphisms in the DNA methyltransferase 3b gene and prostate cancer risk.
Singal R, Das PM, Manoharan M, Reis IM, Schlesselman JJ.
Oncol Rep. 2005 Aug;14(2):569-73.
PMID 16012746
 
DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction.
Suetake I, Shinozaki F, Miyagawa J, Takeshima H, Tajima S.
J Biol Chem. 2004 Jun 25;279(26):27816-23. Epub 2004 Apr 21.
PMID 15105426
 
The role of mammalian DNA methyltransferases in the regulation of gene expression.
Turek-Plewa J, Jagodzinski PP.
Cell Mol Biol Lett. 2005;10(4):631-47.
PMID 16341272
 
A novel C/T polymorphism in the core promoter of human de novo cytosine DNA methyltransferase 3B6 is associated with prognosis in head and neck cancer.
Wang L, Rodriguez M, Kim ES, Xu Y, Bekele N, El-Naggar AK, Hong WK, Mao L, Oh YW.
Int J Oncol. 2004 Oct;25(4):993-9.
PMID 15375549
 
Cloning, expression and chromosome locations of the human DNMT3 gene family.
Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E.
Gene. 1999 Aug 5;236(1):87-95.
PMID 10433969
 
Mutations in DNA methyltransferase DNMT3B in ICF syndrome affect its regulation by DNMT3L.
Xie ZH, Huang YN, Chen ZX, Riggs AD, Ding JP, Gowher H, Jeltsch A, Sasaki H, Hata K, Xu GL.
Hum Mol Genet. 2006 May 1;15(9):1375-85. Epub 2006 Mar 16.
PMID 16543361
 
Genetic variants of methyl metabolizing enzymes and epigenetic regulators: associations with promoter CpG island hypermethylation in colorectal cancer.
de Vogel S, Wouters KA, Gottschalk RW, van Schooten FJ, de Goeij AF, de Bruine AP, Goldbohm RA, van den Brandt PA, Weijenberg MP, van Engeland M.
Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):3086-96. Epub 2009 Oct 20.
PMID 19843671
 

Citation

This paper should be referenced as such :
Ben, Gacem R ; Ben, Abdelkrim O ; Ziadi, S ; Trimeche, M
DNMT3B (DNA (cytosine-5-)-methyltransferase 3 beta)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(2):88-93.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/DNMT3BID40350ch20q11.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(12;12)(p13;q13) ETV6/BAZ2A


External links

Nomenclature
HGNC (Hugo)DNMT3B   2979
LRG (Locus Reference Genomic)LRG_56
Cards
AtlasDNMT3BID40350ch20q11
Entrez_Gene (NCBI)DNMT3B  1789  DNA (cytosine-5-)-methyltransferase 3 beta
AliasesICF; ICF1; M.HsaIIIB
GeneCards (Weizmann)DNMT3B
Ensembl hg19 (Hinxton)ENSG00000088305 [Gene_View]  chr20:31350191-31397162 [Contig_View]  DNMT3B [Vega]
Ensembl hg38 (Hinxton)ENSG00000088305 [Gene_View]  chr20:31350191-31397162 [Contig_View]  DNMT3B [Vega]
ICGC DataPortalENSG00000088305
TCGA cBioPortalDNMT3B
AceView (NCBI)DNMT3B
Genatlas (Paris)DNMT3B
WikiGenes1789
SOURCE (Princeton)DNMT3B
Genetics Home Reference (NIH)DNMT3B
Genomic and cartography
GoldenPath hg19 (UCSC)DNMT3B  -     chr20:31350191-31397162 +  20q11.2   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)DNMT3B  -     20q11.2   [Description]    (hg38-Dec_2013)
EnsemblDNMT3B - 20q11.2 [CytoView hg19]  DNMT3B - 20q11.2 [CytoView hg38]
Mapping of homologs : NCBIDNMT3B [Mapview hg19]  DNMT3B [Mapview hg38]
OMIM242860   602900   
Gene and transcription
Genbank (Entrez)AB208880 AF129267 AF129268 AF129269 AF156487
RefSeq transcript (Entrez)NM_001207055 NM_001207056 NM_006892 NM_175848 NM_175849 NM_175850
RefSeq genomic (Entrez)NC_000020 NC_018931 NG_007290 NT_011362 NW_004929418
Consensus coding sequences : CCDS (NCBI)DNMT3B
Cluster EST : UnigeneHs.713611 [ NCBI ]
CGAP (NCI)Hs.713611
Alternative Splicing GalleryENSG00000088305
Gene ExpressionDNMT3B [ NCBI-GEO ]   DNMT3B [ EBI - ARRAY_EXPRESS ]   DNMT3B [ SEEK ]   DNMT3B [ MEM ]
Gene Expression Viewer (FireBrowse)DNMT3B [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1789
GTEX Portal (Tissue expression)DNMT3B
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UBC3   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UBC3  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UBC3
Splice isoforms : SwissVarQ9UBC3
Catalytic activity : Enzyme2.1.1.37 [ Enzyme-Expasy ]   2.1.1.372.1.1.37 [ IntEnz-EBI ]   2.1.1.37 [ BRENDA ]   2.1.1.37 [ KEGG ]   
PhosPhoSitePlusQ9UBC3
Domaine pattern : Prosite (Expaxy)ADD (PS51533)    C5_MTASE_1 (PS00094)    PWWP (PS50812)    SAM_MT_C5 (PS51679)   
Domains : Interpro (EBI)ADD    C5_DNA_meth_AS    C5_MeTfrase    DNMT3B    PWWP_dom    SAM-dependent_MTases    Znf_FYVE_PHD   
Domain families : Pfam (Sanger)DNA_methylase (PF00145)    PWWP (PF00855)   
Domain families : Pfam (NCBI)pfam00145    pfam00855   
Domain families : Smart (EMBL)PWWP (SM00293)  
Conserved Domain (NCBI)DNMT3B
DMDM Disease mutations1789
Blocks (Seattle)DNMT3B
PDB (SRS)3FLG    3QKJ   
PDB (PDBSum)3FLG    3QKJ   
PDB (IMB)3FLG    3QKJ   
PDB (RSDB)3FLG    3QKJ   
Structural Biology KnowledgeBase3FLG    3QKJ   
SCOP (Structural Classification of Proteins)3FLG    3QKJ   
CATH (Classification of proteins structures)3FLG    3QKJ   
SuperfamilyQ9UBC3
Human Protein AtlasENSG00000088305
Peptide AtlasQ9UBC3
HPRD04209
IPIIPI00012593   IPI00218357   IPI00218358   IPI00218359   IPI00218360   IPI00180702   IPI00909725   IPI00908348   IPI00942456   IPI01009389   
Protein Interaction databases
DIP (DOE-UCLA)Q9UBC3
IntAct (EBI)Q9UBC3
FunCoupENSG00000088305
BioGRIDDNMT3B
STRING (EMBL)DNMT3B
ZODIACDNMT3B
Ontologies - Pathways
QuickGOQ9UBC3
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  response to hypoxia  chromatin binding  transcription corepressor activity  transcription corepressor activity  DNA (cytosine-5-)-methyltransferase activity  DNA (cytosine-5-)-methyltransferase activity  DNA (cytosine-5-)-methyltransferase activity  protein binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  DNA methylation  DNA methylation  DNA-methyltransferase activity  DNA-methyltransferase activity  response to toxic substance  response to ionizing radiation  DNA methylation on cytosine within a CG sequence  positive regulation of gene expression  response to activity  response to caffeine  response to estradiol  response to vitamin A  response to cocaine  response to drug  histone deacetylase binding  intracellular membrane-bounded organelle  unmethylated CpG binding  positive regulation of neuron differentiation  negative regulation of gene expression, epigenetic  S-adenosylhomocysteine metabolic process  S-adenosylmethioninamine metabolic process  metal ion binding  positive regulation of histone H3-K4 methylation  negative regulation of histone H3-K9 methylation  DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates  cellular response to hyperoxia  cellular response to dexamethasone stimulus  C-5 methylation of cytosine  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  response to hypoxia  chromatin binding  transcription corepressor activity  transcription corepressor activity  DNA (cytosine-5-)-methyltransferase activity  DNA (cytosine-5-)-methyltransferase activity  DNA (cytosine-5-)-methyltransferase activity  protein binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  DNA methylation  DNA methylation  DNA-methyltransferase activity  DNA-methyltransferase activity  response to toxic substance  response to ionizing radiation  DNA methylation on cytosine within a CG sequence  positive regulation of gene expression  response to activity  response to caffeine  response to estradiol  response to vitamin A  response to cocaine  response to drug  histone deacetylase binding  intracellular membrane-bounded organelle  unmethylated CpG binding  positive regulation of neuron differentiation  negative regulation of gene expression, epigenetic  S-adenosylhomocysteine metabolic process  S-adenosylmethioninamine metabolic process  metal ion binding  positive regulation of histone H3-K4 methylation  negative regulation of histone H3-K9 methylation  DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates  cellular response to hyperoxia  cellular response to dexamethasone stimulus  C-5 methylation of cytosine  
Pathways : KEGGCysteine and methionine metabolism    MicroRNAs in cancer   
REACTOMEQ9UBC3 [protein]
REACTOME Pathways212300 [pathway]   427413 [pathway]   5334118 [pathway]   
NDEx NetworkDNMT3B
Atlas of Cancer Signalling NetworkDNMT3B
Wikipedia pathwaysDNMT3B
Orthology - Evolution
OrthoDB1789
GeneTree (enSembl)ENSG00000088305
Phylogenetic Trees/Animal Genes : TreeFamDNMT3B
HOVERGENQ9UBC3
HOGENOMQ9UBC3
Homologs : HomoloGeneDNMT3B
Homology/Alignments : Family Browser (UCSC)DNMT3B
Gene fusions - Rearrangements
Fusion : MitelmanDNMT3B/DUSP15 [20q11.21/20q11.21]  
Fusion : MitelmanDNMT3B/MDM4 [20q11.21/1q32.1]  [t(1;20)(q32;q11)]  
Fusion : MitelmanMDM4/DNMT3B [1q32.1/20q11.21]  [t(1;20)(q32;q11)]  
Fusion: TCGADNMT3B 20q11.21 DUSP15 20q11.21 BLCA
Fusion: TCGADNMT3B 20q11.21 MDM4 1q32.1 LAML
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerDNMT3B [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)DNMT3B
dbVarDNMT3B
ClinVarDNMT3B
1000_GenomesDNMT3B 
Exome Variant ServerDNMT3B
ExAC (Exome Aggregation Consortium)DNMT3B (select the gene name)
Genetic variants : HAPMAP1789
Genomic Variants (DGV)DNMT3B [DGVbeta]
DECIPHER (Syndromes)20:31350191-31397162  ENSG00000088305
CONAN: Copy Number AnalysisDNMT3B 
Mutations
ICGC Data PortalDNMT3B 
TCGA Data PortalDNMT3B 
Broad Tumor PortalDNMT3B
OASIS PortalDNMT3B [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICDNMT3B  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDDNMT3B
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
BioMutasearch DNMT3B
DgiDB (Drug Gene Interaction Database)DNMT3B
DoCM (Curated mutations)DNMT3B (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)DNMT3B (select a term)
intoGenDNMT3B
NCG5 (London)DNMT3B
Cancer3DDNMT3B(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM242860    602900   
Orphanet1018   
MedgenDNMT3B
Genetic Testing Registry DNMT3B
NextProtQ9UBC3 [Medical]
TSGene1789
GENETestsDNMT3B
Huge Navigator DNMT3B [HugePedia]
snp3D : Map Gene to Disease1789
BioCentury BCIQDNMT3B
ClinGenDNMT3B
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1789
Chemical/Pharm GKB GenePA27446
Clinical trialDNMT3B
Miscellaneous
canSAR (ICR)DNMT3B (select the gene name)
Probes
Litterature
PubMed279 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineDNMT3B
EVEXDNMT3B
GoPubMedDNMT3B
iHOPDNMT3B
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Apr 12 11:30:45 CEST 2017

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.