Continued activity of the pioneer factor Zelda is required to drive zygotic genome activation
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PROVIDER: PRJNA495878 | ENA |
REPOSITORIES: ENA
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Project description:Reprogramming cell fate during the first stages of embryogenesis requires that transcriptional activators gain access to the genome and remodel the zygotic transcriptome. Nonetheless, it is not clear if the continued activity of these pioneering factors is required throughout zygotic genome activation or if they are only required early to establish cis-regulatory regions. To address this question, we developed an optogenetic strategy to rapidly and reversibly inactivate the master regulator of genome activation in Drosophila, Zelda. Using this strategy, we demonstrated that continued Zelda activity is required throughout genome activation. We showed that Zelda binds DNA in the context of nucleosomes and suggest that this allows Zelda to occupy the genome despite the rapid division cycles in the early embryo. These data identify a powerful strategy to inactivate transcription factor function during development and suggest that reprogramming in the embryo may require specific, continuous pioneering functions to activate the genome.
2019-02-06 | GSE121157 | GEO
Project description:The pioneer transcription factor Zelda (ZLD) increases the accessibility of chromatin to promote the essential process of zygotic genome activation (ZGA) in the Drosophila early embryo. However, many genomic loci remain accessible in the absence of ZLD and are enriched for GA-rich DNA binding motifs. Therefore, we hypothesized that other pioneer TFs that function with ZLD have not yet been identified, especially those that bind to GA-rich motifs. CLAMP (Chromatin-linked adaptor for Male-specific lethal MSL proteins) is a GA-rich motif binding TF that is essential for early embryonic development. Here, we identify for the first time that CLAMP is a pioneer TF which interacts directly with nucleosomes, regulates zygotic genome activation, promotes chromatin accessibility, and facilitates the binding of ZLD to promoters. When ZLD is bound at a locus but does not regulate chromatin accessibility, CLAMP can often function redundantly to open the chromatin. Because ZGA is an essential process across metazoans, it is key to evolve redundant pioneer TFs to protect organisms from lethality that would be caused by loss of a single non-redundant factor.
2021-08-05 | GSE152598 | GEO
Project description:The pioneer transcription factor Zelda (ZLD) increases the accessibility of chromatin to promote the essential process of zygotic genome activation (ZGA) in the Drosophila early embryo. However, many genomic loci remain accessible in the absence of ZLD and are enriched for GA-rich DNA binding motifs. Therefore, we hypothesized that other pioneer TFs that function with ZLD have not yet been identified, especially those that bind to GA-rich motifs. CLAMP (Chromatin-linked adaptor for Male-specific lethal MSL proteins) is a GA-rich motif binding TF that is essential for early embryonic development. Here, we identify for the first time that CLAMP is a pioneer TF which interacts directly with nucleosomes, regulates zygotic genome activation, promotes chromatin accessibility, and facilitates the binding of ZLD to promoters. When ZLD is bound at a locus but does not regulate chromatin accessibility, CLAMP can often function redundantly to open the chromatin. Because ZGA is an essential process across metazoans, it is key to evolve redundant pioneer TFs to protect organisms from lethality that would be caused by loss of a single non-redundant factor.
2021-08-05 | GSE152596 | GEO
Project description:A long-standing question in the field of embryogenesis is how the zygotic genome is precisely activated by maternal factors, allowing normal early embryonic development. We have previously shown that N6-methyladenine (6mA) DNA modification is highly dynamic in early Drosophila embryos and forms an epigenetic mark. However, little is known about how 6mA-formed epigenetic information is decoded. Here we report that the Fox-family protein Jumu binds 6mA-marked DNA and acts as a maternal factor to regulate the maternal-to-zygotic transition. We find that zelda encoding the pioneer factor Zelda is marked by 6mA. Our genetic assays suggest that Jumu controls the proper zygotic genome activation (ZGA) in early embryos, at least in part, by regulating zelda expression. Thus, our findings not only support that the 6mA-formed epigenetic can be read by specific transcription factors, but also uncover a mechanism by which the Jumu regulates ZGA partially through Zelda in early embryos.
2019-04-18 | GSE86795 | GEO
Project description: Not available
| S-EPMC6544384 | biostudies-literature
Project description:During the first stages of development, the fertilized germ cells rapidly transition to totipotency. Maternally deposited mRNAs encode the proteins necessary for reprogramming the transcriptionally quiescent zygotic genome during this maternal-to-zygotic transition (MZT). The transcription factor Zelda is essential for this reprogramming in the Drosophila embryo. Zelda is necessary for transcriptional activation of the zygotic genome, and the absence of Zelda leads to embryonic lethality during the MZT. Excess Zelda activity is also lethal to the embryo, demonstrating that Zelda levels must be precisely controlled during early development. Because Zelda is encoded by a maternally deposited mRNA, Zelda levels in the embryo are controlled at the level of translation. To understand how levels of this essential reprogramming factor were regulated to allow for embryonic development and zygotic genome activation, we investigated the factors that regulated translation of zelda. Brain Tumor (BRAT) is a translational regulator that was previously shown to bind to zelda mRNA in the embryo. We showed that BRAT functions to repress zelda translation, as embryos deficient for maternal BRAT activity prematurely express Zelda. We further showed that in the larval brain, BRAT similarly regulates Zelda levels and identified specific BRAT-binding sites that mediate these effects. Thus, BRAT regulates Zelda in multiple tissues. Because both too little and too much Zelda are lethal to the embryo, we hypothesized that precocious expression of this transcriptional activator might be capable of driving precocious activation of the zygotic genome, leading to embryonic lethality. To test this hypothesis, we performed single embryo RNA-seq at distinct nuclear cycles throughout zygotic genome activation (NC10, NC12, NC13, and NC14) in control and brat-mutant embryos. Our results conclusively demonstrated that in embryos lacking functional BRAT, Zelda target genes were not prematurely activated. Rather, these genes were expressed normally, but become significantly upregulated at nuclear cycle 14, when the division cycle slows. Our data support a model in which zygotic genome activation requires precise coordination between expression of reprogramming factors, such as Zelda, and the slowing of the cell cycle.
2022-06-17 | GSE197582 | GEO
Project description:During early Drosophila embryogenesis, the essential pioneer factor Zelda defines hundreds of cis-regulatory regions and in doing so reprograms the zygotic transcriptome. While Zelda is essential later in development, it is unclear how the ability of Zelda to define cis-regulatory regions is shaped by cell-type specific chromatin architecture established during differentiation. Asymmetric division of neural stem cells (neuroblasts) in the fly brain provide an excellent paradigm for investigating the cell-type specific functions of this pioneer factor. Zelda is expressed in neuroblasts, and we show that Zelda synergistically functions with Notch to maintain neuroblasts in an undifferentiated state. Zelda misexpression can reprogram progenitor cells to neuroblasts, but this capacity is limited by transcriptional repressors critical for progenitor commitment. Zelda genomic occupancy in neuroblasts is reorganized as compared to the embryo, despite sharing many target genes in these two developmental stages. This reorganization is likely driven by differences in chromatin accessibility and cofactor availability. We propose that Zelda regulates essential transitions in the neuroblasts and embryo through a shared gene regulatory network by defining cell-type specific enhancers.
2021-11-05 | GSE150931 | GEO
Project description:Pioneer factors such as Zelda initiate zygotic transcription within Drosophila early embryos, but whether other factors also support this dynamic patterning process is unclear. Odd-paired (Opa) is a zinc-finger transcription factor expressed during cellularization, shown to act as timing factor to control pair-rule to segmental patterning transition along the anterior-posterior (AP) axis. We found Opa regulates expression through an enhancer active along the dorso-ventral axis (sog_Distal), specifically, to support its late embryonic expression. Opa chromatin immunoprecipitation identified occupancy at this enhancer sequence as well widespread binding throughout the genome, comparable to Zelda. Furthermore, chromatin assays (ATAC-seq) demonstrate that Opa, like Zelda, influences accessibility and has both common as well as distinct target sequences. opa mutants also exhibit DV and AP patterning changes suggesting Opa acts broadly. This study suggests Opa is a late-acting, pioneer factor whose action follows Zelda to herald in a second wave of zygotic gene expression. NIH Grants R35GM118146 and R03HD097535 to A.S.
2020-08-02 | GSE140722 | GEO
Project description:CLAMP and Zelda function together as pioneer transcription factors to promote Drosophila zygotic genome activation
| PRJNA639826 | ENA
Project description:Following fertilization, the genomes of the germ cells are reprogrammed to form the totipotent embryo. Pioneer transcription factors are essential for remodeling the chromatin and driving the initial wave of zygotic gene expression. In Drosophila melanogaster, the pioneer factor Zelda is essential for development through this dramatic period of reprogramming, known as the maternal- to-zygotic transition (MZT). However, it was unknown whether additional pioneer factors were required for this transition. We identified an additional maternally encoded factor required for development through the MZT, GAGA Factor (GAF). GAF is necessary to activate widespread zygotic transcription and to remodel the chromatin accessibility landscape. We demonstrated that Zelda preferentially controls expression of the earliest transcribed genes, while genes expressed during widespread activation are predominantly dependent on GAF. Thus, progression through the MZT requires coordination of multiple pioneer-like factors, and we propose that as development proceeds control is gradually transferred from Zelda to GAF.
2021-03-03 | GSE152772 | GEO