Biology subjects

Urban, E.

Publications and source records attributed to Urban, E..

3 recordsLinked to original sources

bioRxiv2021

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

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). Here, we investigated how cis-regulatory elements and trans factors regulate nascent transcriptional activity and chromatin compaction at the ss gene locus during R7 development. We find that the ss locus is in a compact state in undifferentiated cells. An early enhancer drives ss transcription in all R7 precursors to open the ss locus. 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 decompaction and then compaction represses transcription, controls stochastic cell fate specification.

developmental biology↗

bioRxiv2019

Interdependent regulation of stereotyped and stochastic photoreceptor fates in the fly eye

Diversification of neuronal subtypes often requires stochastic gene regulatory mechanisms. How stochastically expressed transcription factors interact with other regulators in gene networks to specify cell fates is poorly understood. The random mosaic of color-detecting R7 photoreceptor subtypes in Drosophila is controlled by the stochastic on/off expression of the transcription factor Spineless (Ss). In SsON R7s, Ss induces expression of Rhodopsin 4 (Rh4), whereas in SsOFF R7s, the absence of Ss allows expression of Rhodopsin 3 (Rh3). Here, we find that the transcription factor Runt, which is initially expressed in all R7s, activates expression of Spineless in a random subset of R7s. Later, as R7s develop, Ss negatively feeds back onto Runt to prevent repression of Rh4 and ensure proper fate specification. Together, stereotyped and stochastic regulatory inputs are integrated into feedforward and feedback mechanisms to control cell fate.

developmental biology↗

bioRxiv2018

Asymmetric histone incorporation during DNA replication in Drosophila male germline stem cells

One Sentence SummaryDNA replication establishes asymmetric epigenomes SummaryOne of the most fundamental questions in developmental biology concerns how cells with identical genomes differentiate into distinct cell types. One important context for understanding cell fate specification is asymmetric cell division, where the two daughter cells establish different cell fates following a single division. Many stem cells undergo asymmetric division to produce both a self-renewing stem cell and a differentiating daughter cell1-5. Here we show that histone H4 is inherited asymmetrically in asymmetrically dividing Drosophila male germline stem cells, similar to H36. In contrast, both H2A and H2B are inherited symmetrically. By combining superresolution microscopy with the chromatin fiber method, we are able to study histone inheritance patterns on newly replicated chromatin fibers. Using this technique, we find asymmetric inheritance patterns for old and new H3, but symmetric inheritance patterns for old and new H2A on replicating sister chromatids. Furthermore, co-localization studies on isolated chromatin fibers and proximity ligation assays on intact nuclei reveal that old H3 are preferentially incorporated by the leading strand while newly synthesized H3 are enriched on the lagging strand. Finally, using a sequential nucleoside analog incorporation assay, we detect a high incidence of unidirectional DNA replication on germline-derived chromatin fibers and DNA fibers. The unidirectional fork movement coupled with the strand preference of histone incorporation could explain how old and new H3 are asymmetrically incorporated by replicating sister chromatids. In summary, our work demonstrates that the intrinsic asymmetries in DNA replication may help construct sister chromatids enriched with distinct populations of histones. Therefore, these results suggest unappreciated roles for DNA replication in asymmetrically dividing cells in multicellular organisms.

developmental biology↗