Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX

摘要: The CXXC domains of TET2 (encoded by the distinct gene IDAX) and TET3 are found to have previously unknown roles in regulation TET proteins through activation caspases subsequent reduction catalytic activity; this is dependent on DNA binding domain. family modify methylation status oxidizing 5-methylcytosine 5-hydroxymethylcytosine (5hmC, sometimes called 'fifth base' DNA) other intermediates. TET1 contain a domain but ancestral encoded gene, IDAX (or CXXC4). This paper demonstrates that binds unmethylated CpG-rich via its recruits TET2. separate linked shown act as regulators caspase enzymatic activity. authors suggest future studies should focus genomic targets TET2, IDAX-related protein CXXC5 normal development cancer. (ten-eleven-translocation) Fe(ii)- α-ketoglutarate-dependent dioxygenases1,2,3 successively 5-hydroxymethylcytosine, 5-formylcytosine 5-carboxycytosine1,3,4,5, potential intermediates active erasure DNA-methylation marks5,6. Here we show (also known CXXC4), reported inhibitor Wnt signalling7 has been implicated malignant renal cell carcinoma8 colonic villous adenoma9, regulates expression. was originally within an underwent chromosomal inversion during evolution, thus separating from sequences containing CpG dinucleotides, localizes promoters islands interacts directly with Unexpectedly, expression results downregulation, manner depends domain, suggesting before degradation. depletion prevents downregulation differentiating mouse embryonic stem cells, short hairpin RNA against increases human monocytic line U937. Notably, find activity also regulated Taken together, these establish TET3, respectively,