PUBLICATION
Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming
- Authors
- Murphy, P.J., Wu, S.F., James, C.R., Wike, C.L., Cairns, B.R.
- ID
- ZDB-PUB-180223-37
- Date
- 2018
- Source
- Cell 172(5): 993-1006.e13 (Journal)
- Registered Authors
- Wu, Shan-Fu
- Keywords
- DNA methylation, H2A.Z, germline-to-embryo transition, zebrafish, zygotic genome activation
- Datasets
- GEO:GSE95031, GEO:GSE95033, GEO:GSE95030, GEO:GSE95032
- MeSH Terms
-
- Animals
- Cellular Reprogramming/genetics*
- DNA Methylation/genetics*
- Embryo, Nonmammalian/metabolism*
- Germ Cells/metabolism*
- Histones/metabolism
- Male
- Mutation/genetics
- Nucleosomes/metabolism*
- Spermatozoa/metabolism
- Zebrafish/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 29456083 Full text @ Cell
Citation
Murphy, P.J., Wu, S.F., James, C.R., Wike, C.L., Cairns, B.R. (2018) Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming. Cell. 172(5):993-1006.e13.
Abstract
The fate and function of epigenetic marks during the germline-to-embryo transition is a key issue in developmental biology, with relevance to stem cell programming and transgenerational inheritance. In zebrafish, DNA methylation patterns are programmed in transcriptionally quiescent cleavage embryos; paternally inherited patterns are maintained, whereas maternal patterns are reprogrammed to match the paternal. Here, we provide the mechanism by demonstrating that "Placeholder" nucleosomes, containing histone H2A variant H2A.Z(FV) and H3K4me1, virtually occupy all regions lacking DNA methylation in both sperm and cleavage embryos and reside at promoters encoding housekeeping and early embryonic transcription factors. Upon genome-wide transcriptional onset, genes with Placeholder become either active (H3K4me3) or silent (H3K4me3/K27me3). Notably, perturbations causing Placeholder loss confer DNA methylation accumulation, whereas acquisition/expansion of Placeholder confers DNA hypomethylation and improper gene activation. Thus, during transcriptionally quiescent gametic and embryonic stages, an H2A.Z(FV)/H3K4me1-containing Placeholder nucleosome deters DNA methylation, poising parental genes for either gene-specific activation or facultative repression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping