Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Pálfy, Máté; Schulze, G; Valen, Eivind; Vastenhouw, Nadine L.

doi:10.1371/journal.pgen.1008546

Cited by 76 publications

(72 citation statements)

References 89 publications

(175 reference statements)

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“…S7a). We concluded that Sox19b binding contributes to establishment of chromatin accessibility during MZT, confirming the results of a previous study 13 .…”

Section: Resultssupporting

confidence: 92%

Pluripotency factors determine gene expression repertoire at zygotic genome activation

Gao

Veil

Rosenblatt

et al. 2020

Preprint

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PouV and SoxB1 family transcription factors (TFs) have emerged as master regulators of cell fate transitions. To investigate the genetic interactions between Pou5f3 and Sox19b in zebrafish embryos passing through Zygotic Genome Activation (ZGA), we combined time-resolved mutant transcription analysis using the novel tool RNA-sense, chromatin state and phenotypic assays. We distinguish four types of embryonic enhancers, differentially regulated by the two TFs. Pou5f3 is critical for activation of enhancer types 1 and 2, which are responsible for transcription of genes involved in gastrulation and ventral genes. Pou5f3 or Sox19b prevent premature activation of type 3 and 4 enhancers, which are responsible for transcription of organogenesis regulators, differentiation factors and dorsal genes. We also show that the balance between Sox19b and Pou5f3 is important for bulk ZGA timing. Our results uncover how independent activities of maternal Pou5f3 and Sox19b add up or antagonize to determine the early gene expression repertoire. Bullet points:• Pou5f3 and Sox19b bind independently to DNA • Disbalance between maternal Pou5f3 and Sox19b delays ZGA • Pou5f3 suppresses premature transcription of neural patterning genes, activated by SoxB1 factors • Pou5f3 and Sox19b synergistically suppress premature transcription of a wide range of differentiation genes • Pou5f3 and Sox19b restrict the dorsal organizer

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“…S7a). We concluded that Sox19b binding contributes to establishment of chromatin accessibility during MZT, confirming the results of a previous study 13 .…”

Section: Resultssupporting

confidence: 92%

Pluripotency factors determine gene expression repertoire at zygotic genome activation

Gao

Veil

Rosenblatt

et al. 2020

Preprint

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“…Indeed, chromatin accessibility profiles of cell types executing similar functions can be highly similar despite showing different expression patterns and being controlled by different master TFs (Maurano et al, 2012;McKay and Lieb, 2013). Moreover, accessibility can signify priming of a locus for expression without commencing transcription (Lara-Astiaso et al, 2014;Pálfy et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Single nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell type-specific gene regulatory variation

Gui

Grzyb

Thomas

et al. 2020

Preprint

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Gui et al.: Single nuclei ATAC-seq of midbrain cell types 2 SUMMARY Cell types in ventral midbrain are involved in diseases with variable genetic susceptibility such as Parkinson's disease and schizophrenia. Many genetic variants affect regulatory regions and alter gene expression. We report 20 658 single nuclei chromatin accessibility profiles of ventral midbrain from two genetically and phenotypically distinct mouse strains.We distinguish ten cell types based on chromatin profiles and analysis of accessible regions controlling cell identity genes highlights cell type-specific key transcription factors.Regulatory variation segregating the mouse strains manifests more on transcriptome than chromatin level. However, cell type-level data reveals changes not captured at tissue level. To discover the scope and cell-type specificity of cis-acting variation in midbrain gene expression, we identify putative regulatory variants and show them to be enriched at differentially expressed loci. Finally, we find TCF7L2 to mediate trans-acting variation selectively in midbrain neurons. Our dataset provides an extensive resource to study gene regulation in mesencephalon.

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“…However, the question to answer remains: what is the mechanism which triggers miR-430 transcription and that of other minor wave transcribed genes? While the stem cell factors Pou5f3/Pou5f1, SoxB1/Sox19b and Nanog were previously shown to be required for miR-430 gene activation (Lee et al , 2013; Miao et al , 2020), they are unlikely to selectively regulate minor wave genome activation, as a large number of major wave genes also depend on these factors (Gao et al , 2020; Lee et al , 2013; Miao et al , 2020; Palfy et al , 2020; Veil et al , 2019).…”

Section: Discussionmentioning

confidence: 99%

“…}. In addition, several molecular mechanisms have been suggested to regulate the timing of genome activation: i) delayed availability of pioneering transcription factors (Lee et al , 2013); ii) or that of the transcription initiation machinery (Bartfai et al , 2004; Ferg et al , 2007; Veenstra et al , 1999); iii) sequential increase in chromatin accessibility (Blythe and Wieschaus, 2016; Palfy et al , 2020); iv) gradual formation of transcriptionally competent chromatin (Lindeman et al , 2011; Chan et al , 2019); v) elongation of the cell cycle, permissive for elongating transcription (Blythe and Wieschaus, 2015; Collart et al , 2013).…”

Section: Introductionmentioning

confidence: 99%

“…MiR-430 activation is dependent on BRD4 and competent chromatin marked by histone H3K27 acetylation (ac) (Chan et al , 2019; Miao et al , 2020) and on the pioneer transcription factors (also called stem cell factors): Nanog, Pou5f3, Sox19b (Chan et al , 2019; Leichsenring et al , 2013; Miao et al , 2020). These stem cell factors have been shown to activate main wave of ZGA in fish (Lee et al , 2013; Leichsenring et al , 2013; Palfy et al , 2020; Veil et al , 2019) and homologs Pou5f3 and Sox3 in Xenopus (Gentsch et al , 2019), while their role in the minor wave of genome activation is not yet understood.…”

Section: Introductionmentioning

confidence: 99%

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The miR-430 locus with extreme promoter density is a transcription body organizer, which facilitates long range regulation in zygotic genome activation

Hadzhiev

Wheatley

Cooper

et al. 2021

Preprint

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In anamniote embryos the major wave of zygotic genome activation (ZGA) starts during the mid-blastula transition. This major wave of ZGA is facilitated by several mechanisms, including dilution of repressive maternal factors and accumulation of activating transcription factors during the fast cell division cycles preceding the mid-blastula transition. However, a set of genes escape global genome repression and are activated substantially earlier, during what is called, the minor wave of genome activation. While the mechanisms underlying the major wave of genome activation have been studied extensively, the minor wave of genome activation is little understood. In zebrafish the earliest expressed RNA polymerase II (Pol II) transcribed genes are activated in a pair of large transcription bodies depleted of chromatin, abundant in elongating Pol II and nascent RNAs (Hadzhiev et al., 2019; Hilbert et al., 2021). This transcription body includes the miR-430 gene cluster required for maternal mRNA clearance. Here we explored the genomic, chromatin organisation and cis-regulatory mechanisms of the minor wave of genome activation occurring in the transcription body. By long read genome sequencing we identified a remarkable cluster of miR-430 genes with over 300 promoters and spanning 0.6 Mb, which represent the highest promoter density of the genome. We demonstrate that the miR-430 gene cluster is required for the formation of the transcription body and acts as a transcription organiser for minor wave activation of a set of zinc finger genes scattered on the same chromosome arm, which share promoter features with the miR-430 cluster. These promoter features are shared among minor wave genes overall and include the TATA-box and sharp transcription start site profile. Single copy miR-430 promoter transgene reporter experiments indicate the importance of promoter-autonomous mechanisms regulating escape from global repression of the early embryo. These results together suggest that formation of the transcription body in the early embryo is the result of high promoter density coupled to a minor wave-specific core promoter code for transcribing key minor wave ZGA genes, which are required for the overhaul of the transcriptome during early embryonic development.

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Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

Cited by 76 publications

References 89 publications

Pluripotency factors determine gene expression repertoire at zygotic genome activation

Pluripotency factors determine gene expression repertoire at zygotic genome activation

Single nuclei chromatin profiling of ventral midbrain reveals cell identity transcription factors and cell type-specific gene regulatory variation

The miR-430 locus with extreme promoter density is a transcription body organizer, which facilitates long range regulation in zygotic genome activation

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