Dataset Information

Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation.

ABSTRACT: The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, but the mechanisms by which this occurs are poorly understood. Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs. Without Zld, Dl binding decreases at enhancers and redistributes to open regions devoid of enhancer activity. We propose that Zld primes enhancers by lowering the high nucleosome barrier just enough to assist TFs in accessing their binding motifs and promoting spatially controlled enhancer activation if the right patterning TFs are present. We envision that genome activators in general will utilize this mechanism to activate the zygotic genome in a robust and precise manner.

SUBMITTER: Sun Y

PROVIDER: S-EPMC4617966 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation.

Sun Yujia Y Nien Chung-Yi CY Chen Kai K Liu Hsiao-Yun HY Johnston Jeff J Zeitlinger Julia J Rushlow Christine C

Genome research 20150902 11

The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, but the mechanisms by which this occurs are poorly understood. Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleoso ...[more]

PMID: 26335633

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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.

Dataset Information

Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation.

Publications

Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation.

Similar Datasets

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