Portal de Periódicos da CAPES

Zelda Potentiates Morphogen Activity by Increasing Chromatin Accessibility

2014; Elsevier BV; Volume: 24; Issue: 12 Linguagem: Inglês

10.1016/j.cub.2014.04.032

1879-0445

Sun Melody Foo, Yujia Sun, Bomyi Lim, Ruta Ziukaite, Kevin O’Brien, Chung-Yi Nien, Nikolai Kirov, Stanislav Y. Shvartsman, Christine Rushlow,

Animal Genetics and Reproduction

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 [1Liang H.L. Nien C.Y. Liu H.Y. Metzstein M.M. Kirov N. Rushlow C. The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila.Nature. 2008; 456: 400-403Crossref PubMed Scopus (318) Google Scholar, 2Nien C.Y. Liang H.L. Butcher S. Sun Y. Fu S. Gocha T. Kirov N. Manak J.R. Rushlow C. Temporal coordination of gene networks by Zelda in the early Drosophila embryo.PLoS Genet. 2011; 7: e1002339Crossref PubMed Scopus (162) Google Scholar, 3Harrison M.M. Li X.Y. Kaplan T. Botchan M.R. Eisen M.B. Zelda binding in the early Drosophila melanogaster embryo marks regions subsequently activated at the maternal-to-zygotic transition.PLoS Genet. 2011; 7: e1002266Crossref PubMed Scopus (210) Google Scholar, 4Lee M.T. Bonneau A.R. Takacs C.M. Bazzini A.A. DiVito K.R. Fleming E.S. Giraldez A.J. Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition.Nature. 2013; 503: 360-364Crossref PubMed Scopus (293) Google Scholar, 5Leichsenring M. Maes J. Mössner R. Driever W. Onichtchouk D. Pou5f1 transcription factor controls zygotic gene activation in vertebrates.Science. 2013; 341: 1005-1009Crossref PubMed Scopus (154) Google Scholar]. Zelda (Zld) plays such a role in the Drosophila embryo, where it has been shown to control the action of patterning signals [1Liang H.L. Nien C.Y. Liu H.Y. Metzstein M.M. Kirov N. Rushlow C. The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila.Nature. 2008; 456: 400-403Crossref PubMed Scopus (318) Google Scholar, 2Nien C.Y. Liang H.L. Butcher S. Sun Y. Fu S. Gocha T. Kirov N. Manak J.R. Rushlow C. Temporal coordination of gene networks by Zelda in the early Drosophila embryo.PLoS Genet. 2011; 7: e1002339Crossref PubMed Scopus (162) Google Scholar]; 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 [6Kanodia J.S. Liang H.L. Kim Y. Lim B. Zhan M. Lu H. Rushlow C.A. Shvartsman S.Y. Pattern formation by graded and uniform signals in the early Drosophila embryo.Biophys. J. 2012; 102: 427-433Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar]. 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 [7Stathopoulos A. Levine M. Genomic regulatory networks and animal development.Dev. Cell. 2005; 9: 449-462Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar, 8Hong J.W. Hendrix D.A. Papatsenko D. Levine M.S. How the Dorsal gradient works: insights from postgenome technologies.Proc. Natl. Acad. Sci. USA. 2008; 105: 20072-20076Crossref PubMed Scopus (97) Google Scholar, 9Reeves G.T. Stathopoulos A. Graded dorsal and differential gene regulation in the Drosophila embryo.Cold Spring Harb. Perspect. Biol. 2009; 1: a000836Crossref Scopus (68) Google Scholar]. 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.