Histone H3R2 symmetric dimethylation and histone H3K4 trimethylation are tightly correlated in eukaryotic genomes.
The preferential in vitro interaction of the PHD finger of RAG2, a subunit of the V(D)J recombinase, with histone H3 tails simultaneously trimethylated at lysine 4 and symmetrically dimethylated at arginine 2 (H3R2me2sK4me3) predicted the existence of the previously unknown histone modification H3R2me2s. Here, we report the in vivo identification of H3R2me2s . Consistent with the binding specificity of the RAG2 PHD finger, high levels of H3R2me2sK4me3 are found at antigen receptor gene segments ready for rearrangement. However, this double modification is much more general; it is conserved throughout eukaryotic evolution. In mouse, H3R2me2s is tightly correlated with H3K4me3 at active promoters throughout the genome. Mutational analysis in S. cerevisiae reveals that deposition of H3R2me2s requires the same Set1 complex that deposits H3K4me3. Our work suggests that H3R2me2sK4me3, not simply H3K4me3 alone, is the mark of active promoters and that factors that recognize H3K4me3 will have their binding modulated by their preference for H3R2me2s.
Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Chih-Chi
CC
Yuan
Adam G W
AG
Matthews
Yi
Y
Jin
Chang Feng
CF
Chen
Brad A
BA
Chapman
Toshiro K
TK
Ohsumi
Karen C
KC
Glass
Tatiana G
TG
Kutateladze
Mark L
ML
Borowsky
Kevin
K
Struhl
Marjorie A
MA
Oettinger
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D056890:Eukaryota / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D056426:Genetic Loci / Q000235:genetics; D016678:Genome / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D011946:Receptors, Antigen / Q000276:immunology; D011995:Recombination, Genetic / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D006657:Histones; D034741:RNA, Small Interfering; D011946:Receptors, Antigen; D029701:Saccharomyces cerevisiae Proteins; D001120:Arginine; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; D008239:Lysine