The maternal to zygotic transition regulates genome-wide heterochromatin establishment in the zebrafish embryo

Abstract

The segregation of eukaryotic genomes into euchromatin and heterochromatin represents a fundamental and poorly understood process. Here, we demonstrate that genome-wide establishment of heterochromatin is triggered by the maternal to zygotic transition (MZT) during zebrafish embryogenesis. We find that prior to MZT, zebrafish lack hallmarks of heterochromatin including histone H3 lysine 9 trimethylation (H3K9me3) and condensed chromatin ultrastructure. Global establishment of heterochromatic features occurs following MZT and requires both activation of the zygotic genome and degradation of maternally deposited RNA. Mechanistically, we demonstrate that zygotic transcription of the micro RNA miR-430 promotes degradation of maternal RNA encoding the chromatin remodeling protein Smarca2, and that clearance of Smarca2 is required for global heterochromatin establishment in the early embryo. Our results identify MZT as a key developmental regulator of heterochromatin establishment during vertebrate embryogenesis and uncover functions for Smarca2 in protecting the embryonic genome against heterochromatinization.

Pervasive non-CpG methylation at zebrafish mosaic satellite repeats

“…We found a clear enrichment of H3K9me3 at methylated MOSAT_DR elements, whereas no other histone modification displayed any signal at these sites ( Fig.2d-e and Additional File1: Figure S5). H3K9me3 has been shown to mark the zebrafish genome pre-ZGA and to progressively increase from ZGA onwards [35,38], however, we find that at a sub-population of MOSAT_DR sites, H3K9me3 is stable during development (256 cell to shield) (Additional File1: Figure S5). This contrasts the observation in mammals, where H3K9me3 and mCH are generally inversely correlated at CG-poor regions [8,29,39].…”

“…4hpf (GSM3484060, GSM3484068), 7hpf (GSM3484061, GSM3484069) and liver (GSM3505059) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122722) [24]. ChIP seq datasets analysed in this study were taken from the following GEO records: H3K9me3 at 6hpf (GSM3096185, GSM3096186), 4.5hpf (GSM3096189, GSM3096190) and 2.5hpf (GSM3096193, GSM3096194) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113086) [35]. H3K27me3 (GSM3165233) and H3K36me3 (GSM3165232) at dome stage (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE114954) [37].…”

“…Finally, we wanted to assess the regulatory environment of mCH-methylated MOSAT motifs. To that end, we analyzed ChIP-seq data of H3K9me3, H3K27me3, H3K36me3, H3K27ac, H3K4me1, and H3K4me3 histone modifications [35][36][37]. We found a clear enrichment of H3K9me3 at methylated MOSAT_DR elements, whereas no other histone modification displayed any signal at these sites ( Fig.2d-e and Additional File1: Figure S5).…”

Extensive nuclear gyration and pervasive non-genic transcription during primordial germ cell development in zebrafish

“…We quantified this using an approach that was recently published (Laue et al, 2019) and found that the level of heterochromatin at 6dpf was significantly lower than at 1 and 3dpf (Figures S1D and E). This suggests that chromatin globally becomes more open at this timepoint.…”

Chromatin Regulates Bipartite-Classified Small RNA Expression to Maintain Epigenome Homeostasis in Arabidopsis

“…Heterochromatin formation is promoted by various pathways including those affecting covalent modifications of histones, which package DNA into nucleosomes, as well as cytosine methylation [5][6][7] . Chromatin states are re-established after fertilization of egg and sperm in diverse animals [8][9][10][11][12] , and histone reprogramming has also been observed in plants shortly after fertilization [13,14] . However, little is known about how heterochromatin-promoting pathways respond to labile chromatin states shortly after fertilization, and help re-establish euchromatic and heterochromatic states in animals and plants.…”