DNA Methylation on N6-Adenine in C. elegans.
In mammalian cells, DNA methylation on the fifth position of cytosine (5mC) plays an important role as an epigenetic mark. However, DNA methylation was considered to be absent in C. elegans because of the lack of detectable 5mC, as well as homologs of the cytosine DNA methyltransferases. Here, using multiple approaches, we demonstrate the presence of adenine N(6)-methylation (6mA) in C. elegans DNA. We further demonstrate that this modification increases trans-generationally in a paradigm of epigenetic inheritance. Importantly, we identify a DNA demethylase, NMAD-1, and a potential DNA methyltransferase, DAMT-1, which regulate 6mA levels and crosstalk between methylations of histone H3K4 and adenines and control the epigenetic inheritance of phenotypes associated with the loss of the H3K4me2 demethylase spr-5. Together, these data identify a DNA modification in C. elegans and raise the exciting possibility that 6mA may be a carrier of heritable epigenetic information in eukaryotes.
Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: eric.greer@childrens.harvard.edu.
Eric Lieberman
EL
Greer
Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Mario Andres
MA
Blanco
Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Lei
L
Gu
Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Erdem
E
Sendinc
Department of Chemistry and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Jianzhao
J
Liu
Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
David
D
Aristizábal-Corrales
Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Chih-Hung
CH
Hsu
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 208943, USA.
L
L
Aravind
Department of Chemistry and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Chuan
C
He
Division of Newborn Medicine, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: yshi@hms.harvard.edu.
Yang
Y
Shi
D000225:Adenine / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D005298:Fertility; D006657:Histones / Q000378:metabolism; D009154:Mutation; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D006657:Histones; D010089:Oxidoreductases, N-Demethylating; C468848:SPR-5 protein, C elegans; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D000225:Adenine