Temporally dynamic antagonism between transcription and chromatin compaction controls stochastic photoreceptor specification in the fly eye

• Published in: Developmental cell Vol. 57; no. 15; pp. 1817 - 1832.e5
• Main Authors: Voortman, Lukas, Anderson, Caitlin, Urban, Elizabeth, Yuan, Rongxin, Tran, Sang, Neuhaus-Follini, Alexandra, Derrick, Josh, Gregor, Thomas, Johnston, Robert J.
• Format: Journal Article
• Language: English
• Published: 13.07.2022
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2022.06.016

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 Ss ON R7s, ss is open and competent for activation by a late enhancer , whereas in Ss OFF 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. Cells sometimes randomly choose between fates during development. In Drosophila, a random mosaic of photoreceptor subtypes is determined by the spineless gene. Voortman et al. find that spineless is regulated by a dynamic interplay between transcription and chromatin compaction during fly eye development.