Tet Proteins Erase Epigenetic Marks

It is (reasonably) common knowledge that DNA is written in a simple four-letter code: ACTG. Too simple, actually.

Tet Proteins Erase Epigenetic MarksIt is (reasonably) common knowledge that DNA is written in a simple four-letter code: ACTG. Too simple, actually. A fifth base—5-methylcytosine 5mC—plays a crucial role in determining which bits of the DNA are actually open for business. Methylation is the basis of the epigenetic marks that control gene activation and with it the differentiation of embryonic stem cells into different tissues and the normal development and functioning of an organism. Differentiated cells can be restored to a state rather like stem cells, so-called induced pluripotent stem cells (iPSCs), suggesting that the epigenetic marks have been removed. And while epigenetic marks may have an impact on future generations, as a result of the way they affect gene functioning, in each generation the marks seem to be completely erased from the primordial germ cells, which go on to form sperm or eggs. What erases the marks? The answer, according to two papers that currently rank among biology’s hottest as tracked by Thomson Reuters Web of Science, is “ten-eleven-translocation” or tet proteins, designated Tet1, Tet2 and Tet3. This newly discovered family of proteins catalyzes the oxidation of 5mC to 5-hydroxymethylcytosine, 5hmC. This (6th) nucleotide base was originally discovered in 1972 but dismissed as the uninteresting result of damage to the DNA. The laboratories of Nat Heintz at Rockefeller University and Anjana Rao at Harvard Medical School re-discovered it in 2009, when Rao’s group showed that Tet1converted 5mC to 5hmC. Then it turned out that mutations in Tet2 were associated with cancers of many kinds of cells in blood, and tumors in general have far less 5mC, which squares with the idea that cancer genes are not being properly regulated. Read more here >>