Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1

Author:

Tahiliani Mamta1,Koh Kian Peng1,Shen Yinghua2,Pastor William A.1,Bandukwala Hozefa1,Brudno Yevgeny2,Agarwal Suneet3,Iyer Lakshminarayan M.4,Liu David R.2,Aravind L.4,Rao Anjana1

Affiliation:

1. Department of Pathology, Harvard Medical School and Immune Disease Institute, 200 Longwood Avenue, Boston, MA 02115, USA.

2. Department of Chemistry and Chemical Biology and the Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.

3. Division of Pediatric Hematology/Oncology, Children’s Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA.

4. National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

Abstract

Methylation Mediation Methylation of cytosine bases, 5-methylcytosine (5mC), in DNA plays an important regulatory role in mammalian genomes. Methylation patterns are often inherited across generations, but they can also be dynamic, suggesting that active DNA demethylation pathways exist. One such pathway, best characterized in plants, involves the removal of the 5mC base, and its replacement by C, via a DNA repair mechanism. Kriaucionis and Heintz (p. 929 , published online 16 April) now show that, as well as 5mC in mammalian genomes, there are also significant amounts of 5-hydroxymethylcytosine (5hmC) in DNA of Purkinje neurons, which have large nuclei with apparently very little heterochromatin. Tahiliani et al. (p. 930, published online 16 April) find that the protein TET1 is capable of converting 5mC into 5hmC both in vitro and in vivo. 5-Hydroxymethylcytosine is also present in embryonic stem cells, and levels of 5hmC and TET1 show correlated variation during cell differentiation.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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