The Drosophila Pioneer Factor Zelda Modulates the Nuclear Microenvironment of a Dorsal Target Enhancer to Potentiate Transcriptional Output

• Published in: Current biology Vol. 29; no. 8; pp. 1387 - 1393.e5
• Main Authors: Yamada, Shigehiro, Whitney, Peter H., Huang, Shao-Kuei, Eck, Elizabeth C., Garcia, Hernan G., Rushlow, Christine A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 22-04-2019
• Subjects: Animals; Cell Nucleus - genetics; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Enhancer Elements, Genetic; enhancer mode; Gene Expression Regulation, Developmental; microenvironment; morphogen gradient; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; pioneer; transcription; Transcription Factors - metabolism; Transcription, Genetic; Transcriptional Activation; Zelda; microenvironment; transcription; pioneer; enhancer mode; Zelda; morphogen gradient
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2019.03.019

Connecting the developmental patterning of tissues to the mechanistic control of RNA polymerase II remains a long-term goal of developmental biology. Many key elements have been identified in the establishment of spatial-temporal control of transcription in the early Drosophila embryo, a model system for transcriptional regulation. The dorsal-ventral axis of the Drosophila embryo is determined by the graded distribution of Dorsal (Dl), a homolog of the nuclear factor κB (NF-κB) family of transcriptional activators found in humans [1, 2]. A second maternally deposited factor, Zelda (Zld), is uniformly distributed in the embryo and is thought to act as a pioneer factor, increasing enhancer accessibility for transcription factors, such as Dl [3–9]. Here, we utilized the MS2 live imaging system to evaluate the expression of the Dl target gene short gastrulation (sog) to better understand how a pioneer factor affects the kinetic parameters of transcription. Our experiments indicate that Zld modifies probability of activation, the timing of this activation, and the rate at which transcription occurs. Our results further show that this effective rate increase is due to an increased accumulation of Dl at the site of transcription, suggesting that transcription factor “hubs” induced by Zld [10] functionally regulate transcription.
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•The expression domain of the Dorsal target gene sog narrows in the absence of Zelda•Using MS2 reporter transgenes, this can be accurately recapitulated in living embryos•Without Zelda, the onset and degree of reporter activation becomes graded like Dorsal•Zelda promotes accumulation of Dorsal protein at the site of the enhancer
Drosophila embryos establish a graded distribution of Dorsal protein to define the dorsal-ventral axis in early development. Yamada, Whitney, et al. demonstrate how Zelda allows a cis-regulatory element to unify gene expression over a broad dynamic range of the Dorsal gradient by raising the local concentration of Dorsal at the enhancer.