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XML generation date: 2024-10-16 17:30:23.305
Product last modified at: 2024-07-17T20:30:09.335Z
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PDP - Template Name: Antibody Sampler Kit
PDP - Template ID: *******4a3ef3a

Human Reactive DNA Demethylation Antibody Sampler Kit #84884

    Product Information

    Product Description

    The Human Reactive DNA Demethylation Antibody Sampler Kit provides an economical means of detecting TET protein family members and TDG protein. The kit includes enough antibodies to perform two western blot experiments with each primary antibody.

    Background

    Methylation of DNA at cytosine residues is a heritable, epigenetic modification that is critical for proper regulation of gene expression, genomic imprinting, and mammalian development (1,2). 5-methylcytosine is a repressive epigenetic mark established de novo by two enzymes, DNMT3a and DNMT3b, and is maintained by DNMT1 (3,4). 5-methylcytosine was originally thought to be passively depleted during DNA replication. However, subsequent studies have shown that Ten-Eleven Translocation (TET) proteins TET1, TET2, and TET3 can catalyze the oxidation of methylated cytosine to 5-hydroxymethylcytosine (5-hmC) (5). Additionally, TET proteins can further oxidize 5-hmC to form 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), both of which are excised by thymine-DNA glycosylase (TDG), effectively linking cytosine oxidation to the base excision repair pathway and supporting active cytosine demethylation (6,7). TET1 is highly expressed in embryonic stem cells and is essential for maintaining stem cell pluripotency (8). Aberrant TET1 expression has also been implicated in a variety of cancers, including hepatocellular carcinoma, T-cell acute lymphoblastic leukemia (T-ALL), and triple-negative breast cancer (TNBC), among others (9-11). TET2 is frequently mutated in myeloid dysplastic syndrome (MDS) and diffuse large B-cell lymphomas (12,13). TET2 protein expression is often reduced in solid tumors such as prostate cancer, melanoma, and oral squamous cell carcinoma (14-16). TET3 plays key roles in regulating early development and neonatal growth (17,18). TET2/TET3 deficiency can lead to myeloid cell, B cell, and invariant natural killer T (iNKT) cell malignancies. In Tregs, TET2/TET3 deficiency in mice leads to hyperproliferation and inflammatory disease (19,20). Knockout or catalytic inactivation of TDG leads to embryonic lethality (21,22). SUMOylation of TDG has been reported to help it dissociate from its abasic product, thereby increasing catalytic turnover (23). Additional studies suggest that SUMOylation affects TDG’s cellular localization or lowers its base excision activity, allowing it to act as a ‘reader’ protein for 5-fC and 5-caC modified DNA (24).
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    9. Shirai, K. et al. (2021) Cancer Sci 112, 2855-2869.
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    12. Langemeijer, S.M. et al. (2009) Nat Genet 41, 838-42.
    13. Asmar, F. et al. (2013) Haematologica 98, 1912-20.
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    16. Jäwert, F. et al. (2013) Anticancer Res 33, 4325-8.
    17. Peat, J.R. et al. (2014) Cell Rep 9, 1990-2000.
    18. Tsukada, Y. et al. (2015) Sci Rep 5, 15876.
    19. Nakatsukasa, H. et al. (2019) Int Immunol 31, 335-347.
    20. Yue, X. et al. (2019) Nat Commun 10, 2011.
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    22. Cortázar, D. et al. (2011) Nature 470, 419-23.
    23. Hardeland, U. et al. (2002) EMBO J 21, 1456-64.
    24. Coey, C.T. and Drohat, A.C. (2018) Nucleic Acids Res 46, 5159-5170.
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