Integrating MNase-seq and RNA-seq Time Series Data to Study Dynamic Chromatin and Transcriptional Regulation Under Cadmium Stress
Though the sequence of the genome is essentially fixed, within each cell it exists in a complex and changing state, determined in part by the dynamic binding of proteins. These proteins—including nucleosomes, transcription factors (TFs), polymerases, and other complexes—define the living chromatin state of the genome. Understanding genome-wide how the dynamics of chromatin interact with the dynamics of transcriptional regulation remains a fundamental research problem. We sought to explore the dynamic connections between chromatin and transcription by treating yeast with cadmium and collecting MNase-seq and RNA-seq data across a 120-minute time course. While gene regulatory responses of cadmium in yeast are generally known, the dynamic chromatin state at regulated genes remains relatively unknown. We were able to identify potential linkages between chromatin and gene regulation, not only at known response genes, but across the entire genome. Combining MNase-seq and RNA-seq data, we found binding signatures of activation and repression involving both nucleosomal and TF-sized DNA binding factors. Using these chromatin signatures, we were able to observe the dynamic interplay of chromatin and transcription over time in response to cadmium stress.