title: Zelda potentiates morphogen activity by increasing chromatin accessibility.
abstract: Zygotic genome activation (ZGA) is a major genome programming event whereby the cells of the embryo begin to adopt specified fates. Experiments in Drosophila and zebrafish have revealed that ZGA depends on transcription factors that provide large-scale control of gene expression by direct and specific binding to gene regulatory sequences. Zelda (Zld) plays such a role in the Drosophila embryo, where it has been shown to control the action of patterning signals; however, the mechanisms underlying this effect remain largely unclear. A recent model proposed that Zld binding sites act as quantitative regulators of the spatiotemporal expression of genes activated by Dorsal (Dl), the morphogen that patterns the dorsoventral axis. Here we tested this model experimentally, using enhancers of brinker (brk) and short gastrulation (sog), both of which are directly activated by Dl, but at different concentration thresholds. In agreement with the model, we show that there is a clear positive correlation between the number of Zld binding sites and the spatial domain of enhancer activity. Likewise, the timing of expression could be advanced or delayed. We present evidence that Zld facilitates binding of Dl to regulatory DNA, and that this is associated with increased chromatin accessibility. Importantly, the change in chromatin accessibility is strongly correlated with the change in Zld binding, but not Dl. We propose that the ability of genome activators to facilitate readout of transcriptional input is key to widespread transcriptional induction during ZGA.
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA.
authors.forename: Sun Melody
authors.initials: SM
authors.lastname: Foo
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Bomyi
authors.initials: B
authors.lastname: Lim
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA.
authors.forename: Ruta
authors.initials: R
authors.lastname: Ziukaite
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Brien
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Nien
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Kirov
authors.affiliation: Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Stanislav Y
authors.initials: SY
authors.lastname: Shvartsman
authors.affiliation: Department of Biology, New York University, New York, NY 10003, USA. Electronic address: chris.rushlow@nyu.edu.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Rushlow
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; C062236:dl protein, Drosophila; C512295:zld protein, Drosophila