Tet1 and 5-hydroxymethylation

Hydroxymethylated Cytosines Are Associated with Elevated C to G Transversion Rates

“…Although coinciding surprisingly poorly with the distribution of 5hmC sites [30], [31], we reasoned that Tet1 binding can be exploited as a sentinel for intrinsic hydroxymethylation risk alongside 5hmC/5mC status itself. 5mC sites can be seen as refractory to hydroxymethylation if they are located inside a Tet1 binding footprint yet fail to show signs of hydroxymethylation.…”

5-hydroxymethyl-cytosine enrichment of non-committed cells is not a universal feature of vertebrate development

“…22,[25][26][27] A recent report suggests that multiple components of the pluripotency network are either novel to mammals or have acquired new expression domains in mammalian development. 28 Since an emerging consensus on a role for 5-hmC in mammalian ESCs implies its participation in maintaining the pluripotency gene regulatory network, 5,[7][8][9] it is therefore possible that 5-hmC enrichment in the DNA of early embryos is also a mammalian innovation and may account for such specific features of the mammalian pluripotency network as the ability to maintain long-term self-renewal, which has been unachievable for non-mammalian ES-like cultures to date. Alternatively, as a recent report brings the perceived role of Tet1, 29 and therefore potentially, 5-hmC during development of mammals into question, our observation that 5-hmC enrichment in non-committed cells is not a universal feature of vertebrate development may contribute to elucidating the role of this modification in mammalian ESCs.…”

“…4,5 5-hmC is produced by enzymatic oxidation of 5-mC, catalyzed by Tet (Ten-11 translocation) proteins (Tet1/2/3), 4,6 which are, according to several reports, important for mouse ESC (mESCs) selfrenewal and/or lineage specification. 4,[7][8][9] Unlike 5-mC, 5-hmC is enriched in both mouse and human ESCs, compared with most differentiated cells. 6,[10][11][12][13] The elevated levels of 5-hmC are lost upon ESC differentiation and reappear during the generation of induced pluripotent stem cells (iPSC); thus, the enrichment of this DNA modification correlates with a pluripotent state.…”

Understanding the structural and dynamic consequences of DNA epigenetic modifications: Computational insights into cytosine methylation and hydroxymethylation

“…9 Even though no protein has been found to interact with hydroxymethylation sites on DNA, 10-11 translocation proteins (TET) have been identified as converters of methylcytosine to hydroxymethylcytosine. 10 Functionally, DNA methylation is crucial for both the developmental and adult stages of an organism. Its presence in highly repetitive sequences makes it a powerful mechanism for gene silencing, in order to maintain genome stability and integrity.…”