H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming.
Histone modifications are central to the regulation of all DNA-dependent processes. Lys64 of histone H3 (H3K64) lies within the globular domain at a structurally important position. We identify trimethylation of H3K64 (H3K64me3) as a modification that is enriched at pericentric heterochromatin and associated with repeat sequences and transcriptionally inactive genomic regions. We show that this new mark is dynamic during the two main epigenetic reprogramming events in mammals. In primordial germ cells, H3K64me3 is present at the time of specification, but it disappears transiently during reprogramming. In early mouse embryos, it is inherited exclusively maternally; subsequently, the modification is rapidly removed, suggesting an important role for H3K64me3 turnover in development. Taken together, our findings establish H3K64me3 as a previously uncharacterized histone modification that is preferentially localized to repressive chromatin. We hypothesize that H3K64me3 helps to 'secure' nucleosomes, and perhaps the surrounding chromatin, in an appropriately repressed state during development.
Daujat
Sylvain
S
Max-Planck-Institute for Immunobiology, Freiburg, Germany.
Weiss
Thomas
T
Mohn
Fabio
F
Lange
Ulrike C
UC
Ziegler-Birling
Céline
C
Zeissler
Ulrike
U
Lappe
Michael
M
Schübeler
Dirk
D
Torres-Padilla
Maria-Elena
ME
Schneider
Robert
R
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000378:metabolism; D044127:Epigenesis, Genetic; D006570:Heterochromatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
D006570:Heterochromatin; D006657:Histones; D009707:Nucleosomes; D012097:Repressor Proteins; D004247:DNA; C498700:Suv39h1 protein, mouse; D008780:Methyltransferases; D008239:Lysine