Differential transcript isoform usage pre- and post-zygotic genome activation in zebrafish

Abstract

BackgroundZebrafish embryos are transcriptionally silent until activation of the zygotic genome during the 10th cell cycle. Onset of transcription is followed by cellular and morphological changes involving cell speciation and gastrulation. Previous genome-wide surveys of transcriptional changes only assessed gene expression levels; however, recent studies have shown the necessity to map isoform-specific transcriptional changes. Here, we perform isoform discovery and quantification on transcriptome sequences from before and after zebrafish zygotic genome activation (ZGA).ResultsWe identify novel isoforms and isoform switches during ZGA for genes related to cell adhesion, pluripotency and DNA methylation. Isoform switching events include alternative splicing and changes in transcriptional start sites and in 3’ untranslated regions. New isoforms are identified even for well-characterized genes such as pou5f1, sall4 and dnmt1. Genes involved in cell-cell interactions such as f11r and magi1 display isoform switches with alterations of coding sequences. We also detect over 1000 transcripts that acquire a longer 3’ terminal exon when transcribed by the zygote compared to their maternal transcript counterparts. ChIP-sequencing data mapped onto skipped exon events reveal a correlation between histone H3K36 trimethylation peaks and skipped exons, suggesting epigenetic marks being part of alternative splicing regulation.ConclusionsThe novel isoforms and isoform switches reported here include regulators of transcriptional, cellular and morphological changes taking place around ZGA. Our data display an array of isoform-related functional changes and represent a valuable resource complementary to existing early embryo transcriptomes.

Dose-dependent effects of gamma radiation on the early zebrafish development and gene expression

“…At this stage the zygotic genome is activated, while the inherited maternal transcript (synthesized during oogenesis and stored in the egg) is degraded [15]. Thus, changes in transcriptome profile can be attributed to radiation effects on the transcriptional program of the embryo’s own genome.…”

Identifying (non‐)coding RNAs and small peptides: Challenges and opportunities

“…The annotation of the zebrafish genome has moved at a rapid pace and offers interesting case studies for distinguishing coding from non‐coding RNAs. Five studies in zebrafish have specifically investigated the coding potential of transcripts, focusing either on identifying non‐coding transcripts , testing and revising previous non‐coding RNA predictions or identifying uncharacterized protein‐coding genes (see Box for details, Fig.…”

“…The annotation of the zebrafish genome has moved at a rapid pace [13][14][15][68][69][70][71][72][73] and offers interesting case studies…”

Functional DNA methylation in a transcript specific 3′UTR region of TrkB associates with suicide

“…Interestingly, the 150 bp sequence of TrkB-T1 3′UTR sequence has been picked up by a CTCF ChIP-seq experiment in human cell lines. 29,30 Furthermore, other epigenetic modifications, such as H3K36me3, 30 which has been suggested to be an epigenetic mark contributing to alternative splicing regulation, 31 have been found in this region. Characterizing CTCF binding sites and mapping H3K36me3 epigenetic marks on TrkB in the frontal cortex of suicide completers could highlight the mechanism by which DNA methylation on TrkB-T1 3′UTR sequence leads to a specific decrease of TrkB-T1 transcript in context of suicide.…”