Tet methylcytosine dioxygenase 1

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TET1
Identifiers
Aliases TET1, CXXC6, LCX, bA119F7.1, MLL-TET1-MLL, Tet methylcytosine dioxygenase 1
External IDs MGI: 1098693 HomoloGene: 12735 GeneCards: TET1
Gene location (Human)
Chromosome 10 (human)
Chr. Chromosome 10 (human)[1]
Chromosome 10 (human)
Genomic location for TET1
Genomic location for TET1
Band 10q21.3 Start 68,560,656 bp[1]
End 68,694,482 bp[1]
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_030625

NM_001253857
NM_027384

RefSeq (protein)

NP_085128

NP_001240786
NP_081660

Location (UCSC) Chr 10: 68.56 – 68.69 Mb Chr 10: 62.8 – 62.91 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is a member of the TET family of enzymes that in humans is encoded by the TET1 gene.[5][6]

Discovery[edit]

TET1 was first discovered in a 61-year-old patient with a rare variation of t(10;11)(q22;q23) acute myeloid leukemia(AML) as a zinc-finger binding protein (specifically on the CXXC domain) that fuses to the gene MLL.[7] Another study confirmed that this protein was a translocation partner of MLL in an 8-year-old patient with t(10;11)(q22;q23) AML and named the protein Ten-Eleven Translocation 1.[8]

Function[edit]

TET1 catalyzes the conversion of the modified DNA base 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC).[9] TET1 produces 5-hmC by oxidation of 5-mC in an iron and alpha-ketoglutarate dependent manner.[10] The conversion of 5-mC to 5-hmC has been proposed as the initial step of active DNA demethylation in mammals.[10] Additionally, downgrading TET1 has decreased levels of 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC) in both cell cultures and mice.[10]

Applications[edit]

TET1 appears to facilitate nuclear reprogramming of somatic cells to iPS cells.[11][12]

Clinical significance[edit]

Patients with schizophrenia or bipolar disorder have shown increased levels of TET1 mRNA and protein expression in the inferior parietal lobule, indicating these diseases may be caused by mistakes in gene expression regulation.[13]

Colon, breast, prostate and liver tumors have significantly reduced levels of TET1 compared to the healthy colon cells and normal epithelial colon cells with downgraded TET1 levels have greater levels of proliferation.[14][15][16][17] Additionally, increasing TET1 expression levels in colon cancer cells decreased cell proliferation in both cell cultures and mice through demethylation of promoters of the WNT signaling pathway.[15]

Breast cancer cell lines with silenced TET1 expression have increased rates of invasion and breast cancers that spread to the lymph nodes are characterized by lower TET1 levels.[18] TET1 levels could be used to detect breast cancer metastasis.[18] A histone deacetylase inhibitor Trichostatin A increased levels of TET1 in breast cancer tissues but was a less effective tumor suppressor in patients with low TET1 expression.[19] Breast cancer patients with high TET1 levels had significantly higher survival probabilities than patients with low TET1 levels.[17]

Degradation of TET1 in hypoxia-induced EMT lung cancer cells led to reduced metastasis rates and cells.[20] Healthy cells transitioning to cancer cells have decreased levels of TET1 but decreasing TET1 expression does not lead to malignancy.[21] Cancer cells using the KRAS pathway had decreased invasive potential after reintroducing TET1, likewise downgrading KRAS increased TET1 levels.[22]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000138336 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000047146 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ "Entrez Gene: Tet methylcytosine dioxygenase 1". Retrieved 2012-07-26. 
  6. ^ Coulter JB, O'Driscoll CM, Bressler JP (October 2013). "Hydroquinone increases 5-hydroxymethylcytosine formation through ten eleven translocation 1 (TET1) 5-methylcytosine dioxygenase". The Journal of Biological Chemistry. 288 (40): 28792–800. doi:10.1074/jbc.M113.491365. PMC 3789975Freely accessible. PMID 23940045. 
  7. ^ Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y (July 2002). "LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23)". Cancer Research. 62 (14): 4075–80. PMID 12124344. 
  8. ^ Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR (March 2003). "TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23)". Leukemia. 17 (3): 637–41. doi:10.1038/sj.leu.2402834. PMID 12646957. 
  9. ^ Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A (May 2009). "Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1". Science. 324 (5929): 930–5. doi:10.1126/science.1170116. PMC 2715015Freely accessible. PMID 19372391. 
  10. ^ a b c Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y (September 2011). "Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine". Science. 333 (6047): 1300–3. doi:10.1126/science.1210597. PMC 3495246Freely accessible. PMID 21778364. 
  11. ^ Pera MF (December 2013). "Epigenetics, vitamin supplements and cellular reprogramming". Nature Genetics. 45 (12): 1412–3. doi:10.1038/ng.2834. PMID 24270443. 
  12. ^ Chen J, Gao Y, Huang H, Xu K, Chen X, Jiang Y, Li H, Gao S, Tao Y, Wang H, Zhang Y, Wang H, Cai T, Gao S (March 2015). "The combination of Tet1 with Oct4 generates high-quality mouse-induced pluripotent stem cells". Stem Cells. 33 (3): 686–98. doi:10.1002/stem.1879. PMID 25331067. 
  13. ^ Dong E, Gavin DP, Chen Y, Davis J (2012-09-01). "Upregulation of TET1 and downregulation of APOBEC3A and APOBEC3C in the parietal cortex of psychotic patients". Translational Psychiatry. 2 (9): e159. doi:10.1038/tp.2012.86. PMC 3565208Freely accessible. PMID 22948384. 
  14. ^ Yang H, Liu Y, Bai F, Zhang JY, Ma SH, Liu J, Xu ZD, Zhu HG, Ling ZQ, Ye D, Guan KL, Xiong Y (January 2013). "Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation". Oncogene. 32 (5): 663–9. doi:10.1038/onc.2012.67. PMC 3897214Freely accessible. PMID 22391558. 
  15. ^ a b Neri F, Dettori D, Incarnato D, Krepelova A, Rapelli S, Maldotti M, Parlato C, Paliogiannis P, Oliviero S (August 2015). "TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway". Oncogene. 34 (32): 4168–76. doi:10.1038/onc.2014.356. PMID 25362856. 
  16. ^ Liu C, Liu L, Chen X, Shen J, Shan J, Xu Y, Yang Z, Wu L, Xia F, Bie P, Cui Y, Bian XW, Qian C (2013-05-09). "Decrease of 5-hydroxymethylcytosine is associated with progression of hepatocellular carcinoma through downregulation of TET1". PLoS One. 8 (5): e62828. doi:10.1371/journal.pone.0062828. PMC 3650038Freely accessible. PMID 23671639. 
  17. ^ a b Hsu CH, Peng KL, Kang ML, Chen YR, Yang YC, Tsai CH, Chu CS, Jeng YM, Chen YT, Lin FM, Huang HD, Lu YY, Teng YC, Lin ST, Lin RK, Tang FM, Lee SB, Hsu HM, Yu JC, Hsiao PW, Juan LJ (September 2012). "TET1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases". Cell Reports. 2 (3): 568–79. doi:10.1016/j.celrep.2012.08.030. PMID 22999938. 
  18. ^ a b Sang Y, Cheng C, Tang XF, Zhang MF, Lv XB (2015-01-01). "Hypermethylation of TET1 promoter is a new diagnosic marker for breast cancer metastasis". Asian Pacific Journal of Cancer Prevention. 16 (3): 1197–200. doi:10.7314/apjcp.2015.16.3.1197. PMID 25735355. 
  19. ^ "TET1 partially mediates HDAC inhibitor-induced suppression of breast cancer invasion". www.spandidos-publications.com. Retrieved 2016-04-07. 
  20. ^ Tsai YP, Chen HF, Chen SY, Cheng WC, Wang HW, Shen ZJ, Song C, Teng SC, He C, Wu KJ (2014-01-01). "TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator". Genome Biology. 15 (12): 513. doi:10.1186/s13059-014-0513-0. PMC 4253621Freely accessible. PMID 25517638. 
  21. ^ Kudo Y, Tateishi K, Yamamoto K, Yamamoto S, Asaoka Y, Ijichi H, Nagae G, Yoshida H, Aburatani H, Koike K (April 2012). "Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation". Cancer Science. 103 (4): 670–6. doi:10.1111/j.1349-7006.2012.02213.x. PMID 22320381. 
  22. ^ Wu BK, Brenner C (December 2014). "Suppression of TET1-dependent DNA demethylation is essential for KRAS-mediated transformation". Cell Reports. 9 (5): 1827–40. doi:10.1016/j.celrep.2014.10.063. PMC 4268240Freely accessible. PMID 25466250. 

Further reading[edit]