William Greenleaf - Exploring the Physical Genome

Professor Greenleaf delved into the exploration and discussion of the physical structure of the genome by addressing the question of how differentiated cells determine the correct phenotype they should evince from their genome. Each cell, despite sharing the same genome, can express specific proteins through transcription factors that recognize DNA sequences. The recognition allows cells to perform distinct roles. Greenleaf's team actively investigated the transcriptional mechanism of the genome in this process, aiming to determine the compression, folding, and other aspects of gene fragments and peptide chains that were controlled by transcription factors.
The team has developed a method for identifying open chromatin elements using a transposase. This technique identifies regulatory elements responsible for driving changes in gene expression. Neural network models were trained to predict mutations that had a highly disruptive impact on chromatin. They also used molecular footprinting methods to understand the specific molecular states of regulatory elements. Using these data, they developed a quantitative model capable of understanding the relationship between DNA sequences and the concentrations of relevant molecules. The resulting partition function model can be employed to evaluate the states of promoters and understand the detailed states that lead to gene expression.