Biology subjects

Hauser, Y. P.

Publications and source records attributed to Hauser, Y. P..

3 recordsLinked to original sources

bioRxiv2025

A scheduler for rhythmic gene expression

Genetic oscillators drive precisely timed gene expression, crucial for development and physiology. Using the C. elegans molting clock as a model, we investigate how oscillators can schedule the orderly expression of thousands of genes. Single cell RNA sequencing reveals a broad peak phase dispersion in individual issues, mirrored by rhythmic changes in chromatin accessibility at thousands of regulatory elements identified by time-resolved ATAC-seq. We develop a linear model to predict chromatin dynamics based on the binding of >200 transcription factors. This identifies nine key regulators acting additively to determine the peak phase and amplitude of each regulatory element. Strikingly, these factors can also generate constitutive, non-rhythmic activity through destructive interference. Validating its power, the model accurately predicts the impact of GRH-1/Grainyhead perturbation on both chromatin and transcript dynamics. This work provides a conceptual framework for understanding how combinatorial, non-cooperative transcription factor binding schedules complex gene expression patterns in development and other dynamic biological processes.

systems biology↗

bioRxiv2021

The BLMP-1 transcription factor promotes oscillatory gene expression to achieve timely molting

Gene expression oscillators can coordinate developmental events in space and time. In C. elegans, a gene expression oscillator directs rhythmic accumulation of [~]25% of the transcriptome, and thus thousands of transcripts, presumably to control molting, a process of rhythmic skin regeneration. Recently, a reverse genetic screen identified several transcription factors important for molting. Here, we characterize one of these, BLMP-1, orthologous to the mammalian transcription repressor PRDM1. We find it to be important for timely molting, and oscillatory gene expression. We propose a dual function for BLMP-1 in shaping oscillatory gene expression and coupling it to a set of direct targets, which ensures cuticular integrity. With mammalian PRDM1/BLIMP1 promoting regular cycles of postnatal hair follicle regeneration, our findings point to the possible existence of a fundamentally conserved clock mechanism in control of rhythmic skin regeneration.

developmental biology↗

bioRxiv2019

State transitions of a developmental oscillator

Gene expression oscillators can structure biological events temporally and spatially. Different biological functions benefit from distinct oscillator properties. Thus, finite developmental processes rely on oscillators that start and stop at specific times; a poorly understood behavior. Here, we have characterized a massive gene expression oscillator comprising >3,700 genes in C. elegans larvae. We report that oscillations initiate in embryos, arrest transiently after hatching and in response to perturbation, and cease in adults. Experimental observation of the transitions between oscillatory and non-oscillatory states at a resolution where we can identify bifurcation points reveals an oscillator operating near a Saddle Node on Invariant Cycle (SNIC) bifurcation. These findings constrain the architecture and mathematical models that can represent this oscillator. They also reveal that oscillator arrests occur reproducibly in a specific phase. Since we find oscillations to be coupled to developmental processes, including molting, this characteristic of SNIC bifurcations thus endows the oscillator with the potential to halt larval development at defined intervals, and thereby execute a developmental checkpoint function.

systems biology↗