In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse
Marco Morselli,
William A Pastor,
Barbara Montanini,
Kevin Nee,
Roberto Ferrari,
Kai Fu,
Giancarlo Bonora,
Liudmilla Rubbi,
Amander T Clark,
Simone Ottonello,
Steven E Jacobsen,
Matteo Pellegrini
Affiliations
Marco Morselli
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
William A Pastor
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Barbara Montanini
Biochemistry and Molecular Biology Unit, Department of Life Sciences, Laboratory of Functional Genomics and Protein Engineering, Parma, Italy
Kevin Nee
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Roberto Ferrari
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Kai Fu
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Giancarlo Bonora
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United States
Liudmilla Rubbi
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Amander T Clark
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States
Simone Ottonello
Biochemistry and Molecular Biology Unit, Department of Life Sciences, Laboratory of Functional Genomics and Protein Engineering, Parma, Italy
Steven E Jacobsen
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United States; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
Matteo Pellegrini
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, United States
Methylation of cytosines (5meC) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves of de novo DNA methylation. In vivo mechanisms of DNA methylation establishment are largely uncharacterized. Here, we use Saccharomyces cerevisiae as a system lacking DNA methylation to define the chromatin features influencing the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4 methylation are mutually exclusive and that DNMT3B is co-localized with H3K36 methylated regions. In support of this observation, DNA methylation analysis in yeast strains without Set1 and Set2 shows an increase of relative 5meC levels at the transcription start site and a decrease in the gene-body, respectively. We extend our observation to the murine male germline, where H3K4me3 is strongly anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These results show the importance of H3K36 methylation for gene-body DNA methylation in vivo.
