Transcript accumulation rates in the early C. elegans embryo

Abstract

Dynamic changes in transcription are widespread in developing embryos, where cell cycles are rapid and cell fate decisions need to be made quickly, often before the next cell division. Some fate decisions in the early Caenorhabditis elegans embryo overcome these constraints through the rapid production of high absolute levels of transcription factor mRNAs. Single cell accumulation rates for a small subset of developmental genes are known, but genome-scale measurements are lacking. Furthermore, how different aspects of transcription kinetics are fine-tuned for different genes to achieve the appropriate RNA levels is still being worked out. We describe a novel strategy to analyze single cell RNA sequencing data from the early C. elegans embryo. We estimate the absolute accumulation rates of zygotic genes up to the 16-cell stage and calibrate predicted rates with single molecule transcript imaging. We show that rapid transcript accumulation is common across different cell types and lineages and rates are the highest soon after zygotic transcription begins. High-rate transcription is a characteristic of genes encoding transcription factors with functions in cell fate specification. These genes share common genomic features and are more likely to have undergone recent duplication. We identify core promoter motifs that might drive high absolute RNA accumulation rates. We measured the contributions of core promoter elements to accumulation rate for one rapidly accumulating gene, ceh-51, which is required for mesoderm development. We find that mutating individual motifs modestly decreases the accumulation rate of ceh-51 mRNA, suggesting multifactorial control of transcript accumulation rates. These results are a step towards estimating absolute transcription kinetics during embryonic fate specification and understanding how transcript dosage drives developmental decisions.