Continued Activity of the Pioneer Factor Zelda Is Required to Drive Zygotic Genome Activation

McDaniel, Stephen L.; Gibson, Tyler J.; Schulz, Katharine N.; García, Meilín Fernández; Nevil, Markus; Jain, Siddhant; Lewis, Peter W.; Zaret, Kenneth S.; Harrison, Melissa M.

doi:10.1016/j.molcel.2019.01.014

Cited by 104 publications

(101 citation statements)

References 51 publications

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“…Our findings complement recent work investigating the role of chromatin structure in the onset of competence for inductive signals, including evidence that maternal proteins act as pioneer factors to open chromatin at the onset of zygotic transcription (Gentsch et al, 2019;Jacobs et al, 2018;McDaniel et al, 2019) and confer competence for primary germ layer formation in Xenopus tropicalis embryos (Gentsch et al, 2019;Paraiso et al, 2019), consistent with the original description of pioneer factors as regulators of developmental competence (Zaret, 1999).…”

Section: Discussionsupporting

confidence: 90%

“…Later in the blastula stage, maternal transcription factors including Fox, Sox, and Oct/Pou family members modify chromatin more globally to establish competence for primary germ layer formation (Charney et al, 2017;Gentsch et al, 2019;Paraiso et al, 2019). In a role analogous to maternal transcription factors Zelda and Grainyhead in Drosophila (Jacobs et al, 2018;McDaniel et al, 2019), maternal Sox and Oct/Pou family transcription factors are required for activation of zygotic gene expression in zebrafish and X. tropicalis (Gentsch et al, 2019;Lee et al, 2013;Leichsenring et al, 2013;Paraiso et al, 2019), functioning as pioneer factors that confer competence for inductive signals at the time of zygotic gene activation (Gentsch et al, 2019). However, the mechanisms by which changes in chromatin architecture mediate loss of competence to early inductive signals, including dorsal Wnt signaling, remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Chromatin accessibility and histone acetylation in the regulation of competence in early development

Esmaeili

Blythe²,

Tobias

et al. 2019

Preprint

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As development proceeds, inductive cues are interpreted by competent tissues in a spatially and temporally restricted manner. While key inductive signaling pathways within competent cells are well-described at a molecular level, the mechanisms by which tissues lose responsiveness to inductive signals are not well understood. Localized activation of Wnt signaling before zygotic gene activation in Xenopus laevis leads to dorsal development, but competence to induce dorsal genes in response to Wnts is lost by the late blastula stage. We hypothesize that loss of competence is mediated by changes in histone modifications leading to a loss of chromatin accessibility at the promoters of Wnt target genes. We use ATAC-seq to evaluate genome-wide changes in chromatin accessibility across several developmental stages. Based on overlap with p300 binding, we identify thousands of putative cis-regulatory elements at the gastrula stage, including sites that lose accessibility by the end of gastrulation and are enriched for pluripotency factor binding motifs. Dorsal Wnt target gene promoters are not accessible after the loss of competence in the early gastrula while genes involved in mesoderm and neural crest development maintain accessibility at their promoters. Inhibition of histone deacetylases increases acetylation at the promoters of dorsal Wnt target genes and extends competence for dorsal gene induction by Wnt signaling. Histone deacetylase inhibition, however, is not sufficient to extend competence for mesoderm or neural crest induction. These data suggest that chromatin state regulates the loss of competence to inductive signals in a context-dependent manner.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Chromatin accessibility and histone acetylation in the regulation of competence in early development

Esmaeili

Blythe²,

Tobias

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…Nucleosome positioning plays a dominant role in regulating DNA access by TFs (He et al, 2010;Klemm et al, 2019). The widespread action of sequence-specific TFs during ZGA is thought to reside on their ability to act as pioneer factors, first displacing nucleosomes, so that other TFs can also bind (Iwafuchi-Doi and Zaret, 2016;McDaniel et al, 2019;Schulz et al, 2015;Sun et al, 2015;Veil et al,2019;Palfy et al, 2020). In case of several TFs, like in zebrafish, it remains an open question, how they divide the labor of activating the zygotic genome, as well as the question how their broad pioneer activity at ZGA relates to their different functions during gastrulation, as inferred from mutant phenotypes (Gagnon et al, 2018;Lunde et al, 2004;Okuda et al, 2010;Veil et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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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“…For example, Zld is a pivotal activator of the MZT as it increases accessibility of chromatin at enhancers, to facilitate binding of other transcriptional activators to these DNA sequences and thereby allow initiation of zygotic gene expression (Harrison et al, 2011;Liang et al, 2008;Nien et al, 2011) . Zld binds nucleosomes and is considered a pioneer factor (McDaniel et al, 2019) . Loss of Zld leads to a large-scale, global decrease in zygotic gene expression as many enhancer regions remain inaccessible and thus non-functional (Schulz et al, 2015) .…”

Section: Introductionmentioning

confidence: 99%

Odd-paired is a late-acting pioneer factor coordinating with Zelda to broadly regulate gene expression in early embryos

Koromila

Iwasaki

et al. 2019

Preprint

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Pioneer factors such as Zelda help initiate zygotic transcription in Drosophila early embryos, but whether other factors support this dynamic process is unclear. Odd-paired (Opa), a zinc-finger transcription factor expressed at cellularization, controls transition of genes from pair-rule to segmental patterns along the anterior-posterior axis. Finding that Opa also regulates late expression through enhancer sog_Distal, along the dorso-ventral axis, we hypothesized that Opa acts as a general timing factor. Chromatin-immunoprecipitation (ChIP-seq) confirmed Opa in vivo binding to sog_Distal but also identified widespread binding throughout the genome, comparable to Zelda. Furthermore, chromatin assays (ATAC-seq) demonstrate that Opa, like Zelda, influences chromatin accessibility genome-wide, suggesting both are pioneer factors with common as well as distinct targets. Lastly, embryos lacking opa exhibit widespread, late patterning defects spanning both axes. Collectively, these data suggest Opa, a general timing factor and likely a late-acting pioneer factor, heralds in a secondary wave of zygotic gene expression.

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Continued Activity of the Pioneer Factor Zelda Is Required to Drive Zygotic Genome Activation

Cited by 104 publications

References 51 publications

Chromatin accessibility and histone acetylation in the regulation of competence in early development

Chromatin accessibility and histone acetylation in the regulation of competence in early development

Pluripotency factors determine gene expression repertoire at zygotic genome activation

Odd-paired is a late-acting pioneer factor coordinating with Zelda to broadly regulate gene expression in early embryos

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