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5-hydroxy methyl cytosine (5hmC) is a modification identified in vertebrates several decades ago. More recently, a possible role of 5hmC as an epigenetic modifier and/or transcriptional regulator has started to emerge, with altered levels in early embryonic development, embryonic stem (ES) cell differentiation and tumours (Tahiliani et al, 2009; Yang et al, 2012). The balance between 5hmC and 5-methyl cytosine (5mC) at gene promoters and CpG islands in the genome appears to be linked to pluripotency and lineage commitment of a cell (Ito et al, 2010). However, proteins with 5hmC binding capability have not yet been identified, and it has been proposed that 5hmC may only be a reaction intermediate in the process of demethylation (He et al, 2011; Ito et al, 2011). Over the last few years, ten-eleven translocation (Tet) family proteins have been shown to be responsible for the conversion of 5mC to 5hmC (Iyer et al, 2009; Loenarz and Schofield, 2009; Tahiliani et al, 2009). However, how Tet family proteins and 5hmC are linked to transcriptional regulation is currently not clear.
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