Dynamic Gene Regulation of Chromatin Regulators

Information in biological systems is stored and transmitted not just in genomic sequences, but in the dynamic expression of genetic material. Crucial information affecting developmental, homeostatic, and disease processes can be contained in how quickly and to what extent genes turn on. Furthermore, the input-output properties of genes are well known to be more complex than simple first or second-order kinetic processes, especially in eukaryotic cells. This complexity can be attributed to the fact that the eukaryotic genome is bound to hundreds of different proteins and RNAs that together with the genome comprise chromatin. There is thus strong reason to believe that chromatin regulates and gives rise to the complexity of dynamic gene regulatory properties. Here, we used time-lapse microscopy with an optogenetic tool that allows light-dependent recruitment of chromatin regulators (CR) to a synthetic reporter in Saccharomyces cerevisiae with high (~2 minute) temporal resolution. To gain greater mechanistic insights into the design principles of chromatin regulation and the types of information that may be stored in the dynamic properties of gene regulation, we characterized the kinetic gene activation/repression parameters of over 200 CRs, including histone acetyltransferases, histone deacetylases, transcription regulators, and nucleosome remodelers. Clustering these CRs by their dynamic transcriptional behaviors through gene ontology provides useful mechanistic insights into basic eukaryotic gene regulation and into selecting CRs for engineering chromatin-based transcriptional regulation.