Biology subjects

Li, X.-Y.

Publications and source records attributed to Li, X.-Y..

6 recordsLinked to original sources

bioRxiv2018

Effects of the maternal factor Zelda on zygotic enhancer activity in the Drosophila embryo

The maternal factor Zelda is broadly bound to zygotic enhancers during early fly embryogenesis, and has been shown to be important for the expression of a large number of genes. However, its function remains poorly understood. Here, we carried out detailed analysis of the functional role of Zelda on the activities of a group of enhancers that drive patterned gene expression along the anterior -posterior axis. We found that among these enhancers, only one lost its activity entirely when all its Zelda bind sites were mutated. For all others, mutations of all of their Zelda binding sites only had limited effect, which varied temporally and spatially. These results suggest that Zld may exert a quantitative effect on a broad range of enhancers, which presumably is critical to generate highly diverse spatial and temporal expression patterns for different genes in the developmental gene network in fly embryo. Lastly, we found that the observed effect of Zelda site mutations was much stronger when a mutant enhancer was tested using a BAC based reporter construct than a simple reporter construct, suggesting that the effect of Zld is dependent on chromatin environment.

developmental biology↗

bioRxiv2018

Mutation of sequences flanking and separating transcription factor binding sites in a Drosophila enhancer significantly alter its output

Here we explore how mutating different sequences in an enhancer that regulates patterned gene expression in Drosophila melanogaster embryos can affect its output. We used quantitative imaging to analyze the effects of a wide variety of mutations in the hunchback distal anterior enhancer. This enhancer has been shown to respond to the anterior morphogen Bicoid, but we found that mutations in only one of the five strong Bicoid sites in the enhancer has a significant effect on its binding. The pioneer factor Zelda, which binds to this enhancer and is the only other factor implicated in its activity besides Bicoid. However, we found that mutations of all its sites only has modest effect that is limited to reduction of its output in more posterior regions of the embryo, where Bicoid levels are low. In contrast to the modest effects of mutating known transcription factor binding sites, randomizing the sequences between Zelda and Bicoid sites significantly compromised enhancer activity. Finer mapping suggested that the sequences that determine activity are broadly distributed in the enhancer. Mutations in short sequences flanking Bicoid binding sites have stronger effects than mutations to Bicoid sites themselves, highlighting the complex and counterintuitive nature of the relationship between enhancer sequence and activity.

developmental biology↗

bioRxiv2018

Zelda potentiates transcription factor binding to zygotic enhancers by increasing local chromatin accessibility during early Drosophila melanogaster embryogenesis.

The maternally deposited transcription factor Zelda binds to and is required for the activation of a large number of genes in early Drosophila development, and has been suggested to act as a pioneer factor. In this study, we investigated the temporal dynamics of Zelda binding along with the maternal patterning factors Dorsal and Caudal during early embryogenesis. We found in regions bound by Zelda and either Dorsal or Caudal, Zelda binding was detected, and reached maximum levels, earlier than Caudal and Dorsal, providing support of its role as a pioneer factor. We found that Dorsal and Caudal binding correlated strongly with Zelda binding at mitotic cycle 12, suggesting that Zelda is important for early binding by these factors and early onset of their target gene expression. At the same time, we show that among Dorsal target enhancers, the dorsal and ventral ectoderm enhancers are much more strongly associated with Zelda than mesoderm enhancers, revealing an additional function of Zelda in coordinating spatial activity of enhancers. We have also investigated the role of Zelda on chromatin structure. We found that in early embryos, before Dorsal and Caudal are bound at significant levels, Zelda binding is associated with histone acetylation and local histone depletion. These chromatin associated changes accompanied with increased local chromatin accessibility were also detected around Zelda peaks in coding sequences that do not appear to play a role in subsequent transcription factor binding. These findings suggest that Zelda binding itself can lead to chromatin structural changes. Finally, we found that Zelda motifs, both bound and unbound, tend to be associated with positioned nucleosomes, which we suggest may be important for the regulatory specificity of enhancers.

developmental biology↗

bioRxiv2017

Temperate phages as frequency-dependent weapons in bacterial competition

Microbial communities are accompanied by a diverse array of viruses. Through infections of abundant microbes, these viruses have the potential to mediate competition within the community, effectively weakening competitive interactions and promoting coexistence. This is of particular relevance for host-associated microbial communities, since the diversity of the microbiota has been linked to host health and functioning. Here, we study the interaction between two key members of the microbiota of the freshwater metazoan Hydra vulgaris. The two commensal bacteria Curvibacter sp. and Duganella sp. protect their host from fungal infections, but only if both of them are present. Coexistence of the two bacteria is thus beneficial for Hydra. Intriguingly, Duganella sp. appears to be the superior competitor in vitro due to its higher growth rate when both bacteria are grown seperately, but in coculture the outcome of competition depends on the relative initial abundances of the two species. The presence of an inducible prophage in the Curvibacter sp. genome which is able to lytically infect Duganella sp., led us to hypothesise that the phage modulates the interaction between these two key members of the Hydra microbiota. Using a mathematical model we show that the interplay of the lysogenic life-cycle of the Curvibacter phage and the lytic life-cycle on Duganella sp. can explain the observed complex competitive interaction between the two bacteria. Our results highlight the importance of taking lysogeny into account for understanding microbe-virus interactions and show the complex role phages can play in promoting coexistence of their bacterial hosts.

microbiology↗

bioRxiv2017

Dense Bicoid Hubs Accentuate Binding along the Morphogen Gradient

Morphogen gradients direct the spatial patterning of developing embryos, however, the mechanisms by which these gradients are interpreted remain elusive. Here we perform in vivo single molecule imaging in early Drosophila melanogaster embryos of the transcription factor Bicoid that forms a gradient and initiates patterning along the anteroposterior axis. We observe that Bicoid binds to DNA with a rapid off-rate, such that its average occupancy at target loci is on-rate dependent, a property required for concentration-sensitive regulation. Surprisingly, we also observe abundant specific DNA binding in posterior nuclei, where Bicoid levels are vanishingly low. Live embryo imaging reveals spatiotemporal \"hubs\" of local high Bicoid concentration that are dependent on the ubiquitous maternal factor Zelda. We propose that localized modulation of transcription factor on-rates via clustering, provides a general mechanism to facilitate binding to low-affinity targets, and that this may be a prevalent feature directing other developmental transcription networks.

developmental biology↗

bioRxiv2017

Sexual reproduction as bet-hedging

In evolutionary biology, bet-hedging refers to a strategy that reduces the variance of reproductive success at the cost of reduced mean reproductive success. In unpredictably fluctuating environments, bet-hedgers benefit from higher geometric mean fitness despite having lower arithmetic mean fitness than their specialist competitors. We examine the extent to which sexual reproduction can be considered a type of bet-hedging, by clarifying past arguments, examining parallels and differences to evolutionary games, and by presenting a simple model examining geometric and arithmetic mean payoffs of sexual and asexual reproduction. Sex typically has lower arithmetic mean fitness than asex, while the geometric mean fitness can be higher if sexually produced offspring are not identical. However, asexual individuals that are heterozygotes can gain conservative bet-hedging benefits of similar magnitude while avoiding the costs of sex. This highlights that bet-hedging always has to be specified relative to the payoff structure of relevant competitors. It also makes it unlikely that sex, at least when associated with significant male production, evolves solely based on bet-hedging in the context of frequently and repeatedly occupied environmental states. Future work could usefully consider bet-hedging in open-ended evolutionary scenarios with de novo mutations.

evolutionary biology↗