H3K64me3 and H3K9me3 profiling at promoters in mouse embryonic stem cells

ABSTRACT: Histone modifications are central to the regulation of all DNA-dependent processes but the repertoire of known modifications is far from complete. Lysine 64 of Histone H3 (H3K64) lies within the globular domain of H3 at a structurally important position within the nucleosome. We identify tri-methylation of H3K64 (H3K64me3) as a modification enriched in pericentric heterochromatin and associated with repeated sequences and transcriptionally inactive genomic regions. Interestingly, the pericentric enrichment of H3K64me3 depends on the Suv39h methyltransferases. Further, we show that this newly identified mark is dynamically regulated during the two major epigenetic reprogramming events in mammals. In primordial germ cells (PGCs) H3K64me3 is present at the time of specification, but disappears transiently during germline reprogramming. In the early mouse embryo it is inherited exclusively through the maternal germline and specifically enriched in heterochromatic regions of the maternal pronucleus. Subsequently the modification is rapidly removed from the maternal chromatin suggesting an important role for H3K64me3 turnover in development. Taken together, our findings firmly establish H3K64me3 as a novel histone modification mark of repressive chromatin, which displays crosstalk to the Suv39 pathway and is dynamically reprogrammed during development. We hypothesize that methylation of this lysine helps to 'secure' the nucleosome and perhaps the surrounding heterochromatin, in an appropriately repressed state during development. Keywords: ChIP-chip, embryonic stem cells, H3K64me3, H3K9me3, heterochromatin ChIP-chip experiments were performed with four independent biological replicates for H3K64me3 and two independent replicates for H3K9me3. For each condition hybridizations include a dye-swap experiment.

ORGANISM(S): Mus musculus

SUBMITTER: Robert Schneider 

PROVIDER: E-GEOD-16185 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress