Tet proteins are emerging as major epigenetic modulators of cell fate and plasticity. However, little is known about how Tet proteins are targeted to selected genomic loci in distinct biological contexts. Previously, a CXXC-type zinc finger domain in Tet1 was shown to bind CpG-rich DNA sequences. Interestingly, in human and mouse the Tet2 and Tet3 genes are adjacent to Cxxc4 and Cxxc10-1, respectively. The CXXC domains encoded by these loci, together with those in Tet1 and Cxxc5, identify a distinct homology group within the CXXC domain family. Here we provide evidence for alternative mouse Tet3 transcripts including the Cxxc10-1 sequence (Tet3(CXXC)) and for an interaction between Tet3 and Cxxc4. In vitro Cxxc4 and the isolated CXXC domains of Tet1 and Tet3(CXXC) bind DNA substrates with similar preference towards the modification state of cytosine at a single CpG site. In vivo Tet1 and Tet3 isoforms with and without CXXC domain hydroxylate genomic 5-methylcytosine with similar activity. Relative transcript levels suggest that distinct ratios of Tet3(CXXC) isoforms and Tet3-Cxxc4 complex may be present in adult tissues. Our data suggest that variable association with CXXC modules may contribute to context specific functions of Tet proteins.
Pubmed ID: 23690950 RIS Download
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German research awards.Central self governing research funding organisation in Germany. Serves sciences and humanities and promotes research at universities and non-university research institutions. The focus is on funding projects developed by academic community.
View all literature mentionsGerman research awards.Central self governing research funding organisation in Germany. Serves sciences and humanities and promotes research at universities and non-university research institutions. The focus is on funding projects developed by academic community.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line C2C12 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis unknown targets Mouse Rat radial glial cell marker
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