@article{fa59906965a64d6a8287701002d99da5,
title = "Temporally dynamic antagonism between transcription and chromatin compaction controls stochastic photoreceptor specification in flies",
abstract = "Stochastic mechanisms diversify cell fates during development. How cells randomly choose between two or more fates remains poorly understood. In the Drosophila eye, the random mosaic of two R7 photoreceptor subtypes is determined by expression of the transcription factor Spineless (Ss). We investigated how cis-regulatory elements and trans factors regulate nascent transcriptional activity and chromatin compaction at the ss gene locus during R7 development. The ss locus is in a compact state in undifferentiated cells. An early enhancer drives transcription in all R7 precursors, and the locus opens. In differentiating cells, transcription ceases and the ss locus stochastically remains open or compacts. In SsON R7s, ss is open and competent for activation by a late enhancer, whereas in SsOFF R7s, ss is compact, and repression prevents expression. Our results suggest that a temporally dynamic antagonism, in which transcription drives large-scale decompaction and then compaction represses transcription, controls stochastic fate specification.",
keywords = "Ash2, Drosophila, Klumpfuss, Lid, Spineless, chromatin, enhancer, photoreceptor, retina, stochastic",
author = "Lukas Voortman and Caitlin Anderson and Elizabeth Urban and Luorongxin Yuan and Sang Tran and Alexandra Neuhaus-Follini and Josh Derrick and Thomas Gregor and Johnston, {Robert J.}",
note = "Funding Information: We thank the JHU integrated Imaging Center. We thank Andre Bedard, Judith Kasis, Kami Ahmed, Jessica Treisman, and Claude Desplan for antibodies and fly lines; Andrew Gordus for input on statistical analysis; and Claude Desplan, and Luisa Cochella, for feedback on the manuscript. This work was supported by NIH F31EY032430 (L.V.); NIH F31EY031963 (E.U.); NSF PHY-1734030 , NIH R01GM097275 , and NIH U01DA047730 (T.G.); and NIH R01EY025598 (R.J.J.). Funding Information: We thank the JHU integrated Imaging Center. We thank Andre Bedard, Judith Kasis, Kami Ahmed, Jessica Treisman, and Claude Desplan for antibodies and fly lines; Andrew Gordus for input on statistical analysis; and Claude Desplan, and Luisa Cochella, for feedback on the manuscript. This work was supported by NIH F31EY032430 (L.V.); NIH F31EY031963 (E.U.); NSF PHY-1734030, NIH R01GM097275, and NIH U01DA047730 (T.G.); and NIH R01EY025598 (R.J.J.). Conceptualization, L.V. C.A. and R.J.J.; methodology, L.V. and C.A.; software, L.V. and T.G.; validation, L.V. and C.A.; formal analysis, L.V.; investigation, L.V. C.A. E.U. R.Y. S.T. A.N.-F. and J.D.; writing—original draft preparation, L.V. C.A. and R.J.J.; writing—review and editing, L.V. and R.J.J.; visualization, L.V. C.A. and R.J.J.; supervision, R.J.J.; project administration, R.J.J.; funding acquisition, R.J.J. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = aug,
day = "8",
doi = "10.1016/j.devcel.2022.06.016",
language = "English (US)",
volume = "57",
pages = "1817--1832.e5",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "15",
}