Temporally dynamic antagonism between transcription and chromatin compaction controls stochastic photoreceptor specification in flies

• Published in: Developmental cell Vol. 57; no. 15; pp. 1817 - 1832.e5
• Main Authors: Voortman, Lukas, Anderson, Caitlin, Urban, Elizabeth, Yuan, Luorongxin, Tran, Sang, Neuhaus-Follini, Alexandra, Derrick, Josh, Gregor, Thomas, Johnston, Robert J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.08.2022; Elsevier
• Subjects: Animal genetics; Animals; Ash2; Biochemistry, Molecular Biology; Biophysics; chromatin; Chromatin - genetics; Chromatin - metabolism; Development Biology; Drosophila; Drosophila - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; enhancer; Gene Expression Regulation, Developmental; Genetics; Klumpfuss; Lid; Life Sciences; photoreceptor; Photoreceptor Cells, Invertebrate - metabolism; retina; Spineless; stochastic; Transcription Factors - genetics; Transcription Factors - metabolism; enhancer; Ash2; Spineless; retina; Drosophila; Lid; photoreceptor; stochastic; Klumpfuss; chromatin
• 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 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. [Display omitted] •spineless is off, and the locus is in a compact state in undifferentiated cells•The early enhancer drives expression, and the locus opens•Expression ceases, and the locus recompacts or remains open•Repression in a subset of R7s limits expression driven by the late enhancer 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.