Uncoupled H3K9me3 nucleation and reinforcement during early zebrafish embryogenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1078867 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28037600_1.fastq.gz | Fastqsanger.gz | |||
| SRR28037600_2.fastq.gz | Fastqsanger.gz | |||
| SRR28037601_1.fastq.gz | Fastqsanger.gz | |||
| SRR28037601_2.fastq.gz | Fastqsanger.gz | |||
| SRR28037602_1.fastq.gz | Fastqsanger.gz |
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Project description:The structural organization of eukaryotic genomes is contingent upon fractionation of DNA into transcriptionally active euchromatin and repressive heterochromatin. However, we still have a limited understanding of how these distinct states are first established during animal embryogenesis. Histone lysine 9 trimethylation (H3K9me3) is critical to heterochromatin formation and bulk establishment of this mark is thought to help drive large-scale remodeling of the initially naive chromatin state during animal embryogenesis. However, a detailed understanding of this process is lacking. Here, we leverage CUT&RUN to define the emerging H3K9me3 landscape of the zebrafish embryo with high sensitivity and temporal resolution. We find that despite the prevalence of DNA transposons in the zebrafish genome, LTR transposons are preferentially targeted for H3K9me3 deposition in the embryo, with different families showing distinct establishment kinetics. High signal-to-noise ratios afforded by CUT&RUN revealed emerging sites of low-amplitude H3K9me3 nucleation prior embryonic genome activation (EGA), with early nucleation primarily at a subset of transposon sequences, loci enriched for maternal piRNAs, and pericentromeres. Unexpectedly, the number of nucleated H3K9me3 sites increases linearly across blastula development while quantitative comparison revealed a >10-fold genome-wide increase in H3K9me3 signal at established sites over just 30 minutes precisely at the onset of major EGA. Later stage analysis revealed continued maturation of the H3K9me3 landscape beyond the initial wave of bulk establishment. Our findings uncover distinct mechanisms of pre- and post-EGA H3K9me3 targeting and reveal decoupling of H3K9me3 establishment from reinforcement during de novo heterochromatin formation.
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Project description:The structural organization of eukaryotic genomes is contingent upon the fractionation of DNA into transcriptionally active euchromatin and repressive heterochromatin. However, we have a limited understanding of how these distinct states are first established during animal embryogenesis. Histone 3 lysine 9 trimethylation (H3K9me3) is critical to heterochromatin formation and bulk establishment of this mark is thought to help drive large-scale remodeling of an initially naive chromatin state during animal embryogenesis. However, a detailed understanding of this process is lacking. Here, we leverage CUT&RUN to define the emerging H3K9me3 landscape of the zebrafish embryo with high sensitivity and temporal resolution. Despite the prevalence of DNA transposons in the zebrafish genome, we found that LTR transposons are preferentially targeted for embryonic H3K9me3 deposition, with different families exhibiting distinct establishment timelines. High signal-to-noise ratios afforded by CUT&RUN revealed new, emerging sites of low-amplitude H3K9me3 that initiated before the major wave of embryonic genome activation (EGA). Early sites of establishment predominated at specific subsets of transposons and were enriched for sequences with maternal piRNAs or pericentromeric localization. Notably, the number of H3K9me3 enriched sites increased linearly across blastula development, while quantitative comparison revealed a >10-fold genome-wide increase in H3K9me3 signal at established sites over just 30 minutes at the onset of EGA. Continued maturation of the H3K9me3 landscape was observed beyond the initial wave of bulk establishment. Our findings uncover distinct features of pre- and post-EGA H3K9me3 targeting and reveal temporal decoupling of H3K9me3 establishment and signal reinforcement during zebrafish heterochromatin formation.
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