Prepatterning of Developmental Gene Expression by Modified Histones before Zygotic Genome Activation

Abstract

A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive role of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles provides an opportunity to examine whether genomic enrichment in modified histones is present before initiation of transcription. By profiling histone H3 trimethylation on all zebrafish promoters before and after ZGA, we demonstrate here an epigenetic prepatterning of developmental gene expression. This involves pre-ZGA marking of transcriptionally inactive genes involved in homeostatic and developmental regulation by permissive H3K4me3 with or without repressive H3K9me3 or H3K27me3. Our data suggest that histone modifications are instructive for the developmental gene expression program.

Emerging Role of the Peroxisome Proliferator-Activated Receptors in Hepatocellular Carcinoma

“…A similar observation was made in zebra fish sperm, in which genes activated after mid-blastula transition are pre-patterned by specific histone modifications [64]. However, the dynamic or unstable nature of epigenetic marks present in the sperm is indicated by the low levels of histone modifications in pre-mid-blastula transition after fertilization [65,66].The insights into the remodelling of epigenetic marks at enhancers during normal development might be applicable to the understanding of the mechanisms underlying the establishment of iPSCs. These cells can be obtained through the reprogramming of somatic cells by ectopic expression of defined transcription factors [67].…”

Parental epigenetic control of embryogenesis: a balance between inheritance and reprogramming?

“…In zebrafish embryos, homeostatic and developmentally regulated genes are marked by permissive and repressive histone modifications prior to zygotic genome activation. This pre-patterning reflects in part chromatin marking observed in zebrafish sperm, providing means for intergenerational inheritance [11], [12]. In the context of RNA-based inheritance, transmission of silencing induced by siRNAs (for instance in C. elegans) [13] or maternal piRNAs (in Drosophila) [14]) has also been established.…”

Haploid selection within a single ejaculate increases offspring fitness

“…Sperm aging, before or after ejaculation, may affect the epigenetic composition of the sperm (19) and/or the quality of sperm DNA by inducing deleterious mutations (20,21) that may, in turn, affect the development of the resulting zygote. For experiment 2, we investigated the possibility of preejaculation sperm aging by collecting consecutive sperm subsamples, each containing 0.8 μL of ejaculate, until the male had no more sperm; thus the first subsample contained the oldest sperm, and the last sample contained the youngest (see SI Materials and Methods for details).…”