DNMT3B
DNMT3B（DNA (cytosine-5-)-methyltransferase 3 beta）は、ヒトではDNMT3B遺伝子によってコードされる酵素である[5]。この遺伝子の変異は、ICF症候群と関係している[6]。
機能
[編集]CpGのメチル化は、胚発生、インプリンティング、X染色体の不活性化に重要なエピジェネティック修飾である。マウスでの研究では、DNAのメチル化は哺乳類の発生に必要であることが実証されている。DNMT3B遺伝子はDNAメチルトランスフェラーゼをコードし、維持メチル化ではなくde novoメチル化に機能すると考えられている。DNMT3Bタンパク質は主に核内に局在し、その発現は発生過程で調節されている。選択的スプライシングによる8種類の転写バリアントが記載されているが、バリアント4とバリアント5の全長配列は未決定である[5]。
臨床的意義
[編集]ICF症候群は、DNMT3B遺伝子の変異によるDNAメチル化の異常の結果生じる、リンパ球の成熟の欠陥を原因とする[6]。
この遺伝子のバリアントはニコチン依存症にも寄与している[7]。
相互作用
[編集]DNMT3Bは次に挙げる因子と相互作用することが示されている。
出典
[編集]- ^ a b c GRCh38: Ensembl release 89: ENSG00000088305 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027478 - Ensembl, May 2017
- ^ Human PubMed Reference:
- ^ Mouse PubMed Reference:
- ^ a b “Entrez Gene: DNMT3B DNA (cytosine-5-)-methyltransferase 3 beta”. 2021年8月7日閲覧。
- ^ a b “The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease”. Clinical Immunology 109 (1): 17–28. (October 2003). doi:10.1016/S1521-6616(03)00201-8. PMID 14585272.
- ^ “Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence”. Molecular Psychiatry 23 (9): 1911–1919. (October 2017). doi:10.1038/mp.2017.193. PMC 5882602. PMID 28972577.
- ^ a b c “Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin”. Current Biology 13 (14): 1192–200. (July 2003). doi:10.1016/s0960-9822(03)00432-9. PMID 12867029.
- ^ a b “Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases”. The EMBO Journal 21 (15): 4183–95. (August 2002). doi:10.1093/emboj/cdf401. PMC 126147. PMID 12145218.
- ^ “Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription”. Nucleic Acids Research 32 (2): 598–610. (2004). doi:10.1093/nar/gkh195. PMC 373322. PMID 14752048.
- ^ a b c “Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery”. Nucleic Acids Research 32 (9): 2716–29. (2004). doi:10.1093/nar/gkh589. PMC 419596. PMID 15148359.
- ^ a b “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. (December 2001). doi:10.1006/bbrc.2001.6057. PMID 11735126.
関連文献
[編集]- “Genetic variation in ICF syndrome: evidence for genetic heterogeneity”. Human Mutation 16 (6): 509–17. (December 2000). doi:10.1002/1098-1004(200012)16:6<509::AID-HUMU8>3.0.CO;2-V. PMID 11102980.
- “Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases”. Nature Genetics 19 (3): 219–20. (July 1998). doi:10.1038/890. PMID 9662389.
- “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. (June 1999). doi:10.1093/nar/27.11.2291. PMC 148793. PMID 10325416.
- “Cloning, expression and chromosome locations of the human DNMT3 gene family”. Gene 236 (1): 87–95. (August 1999). doi:10.1016/S0378-1119(99)00252-8. PMID 10433969.
- “DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development”. Cell 99 (3): 247–57. (October 1999). doi:10.1016/S0092-8674(00)81656-6. PMID 10555141.
- “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. (December 1999). doi:10.1073/pnas.96.25.14412. PMC 24450. PMID 10588719.
- “Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene”. Nature 402 (6758): 187–91. (November 1999). doi:10.1038/46052. PMID 10647011.
- “DNA cloning using in vitro site-specific recombination”. Genome Research 10 (11): 1788–95. (November 2000). doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- “Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription”. The EMBO Journal 20 (10): 2536–44. (May 2001). doi:10.1093/emboj/20.10.2536. PMC 125250. PMID 11350943.
- “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. (December 2001). doi:10.1006/bbrc.2001.6057. PMID 11735126.
- “DNMT1 and DNMT3b cooperate to silence genes in human cancer cells”. Nature 416 (6880): 552–6. (April 2002). doi:10.1038/416552a. PMID 11932749.
- “Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice”. Development 129 (8): 1983–93. (April 2002). PMID 11934864.
- “An essential role for DNA methyltransferase DNMT3B in cancer cell survival”. The Journal of Biological Chemistry 277 (31): 28176–81. (August 2002). doi:10.1074/jbc.M204734200. PMID 12015329.
- “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. (July 2002). doi:10.1073/pnas.152121799. PMC 126624. PMID 12110732.
- “Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases”. The EMBO Journal 21 (15): 4183–95. (August 2002). doi:10.1093/emboj/cdf401. PMC 126147. PMID 12145218.
- “Dnmt3L is a transcriptional repressor that recruits histone deacetylase”. Nucleic Acids Research 30 (17): 3831–8. (September 2002). doi:10.1093/nar/gkf509. PMC 137431. PMID 12202768.
- “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. (September 2002). PMID 12208751.
- “Three novel DNMT3B mutations in Japanese patients with ICF syndrome”. American Journal of Medical Genetics 112 (1): 31–7. (September 2002). doi:10.1002/ajmg.10658. PMID 12239717.