Interview for Faculty Position

How the packaging of DNA influences gene expression

Harold D. Kim

Departments of Molecular and Cellular Biology & Chemistry and Chemical Biology
Harvard University

Transcription factors are regulatory proteins that bind to specific DNA sequences upstream of a gene and influence transcription. However, binding of transcription factors can be hindered because DNA in eukaryotes (for example, yeast, humans, etc) is highly compacted into nucleosomes; very much like winding a string around a bead. This problem is further complicated by the fact that there are often multiple transcription binding sites per gene with different binding affinities. Therefore, it remains a challenge to understand how this variable interaction between transcription factors and DNA contributes to a fine-tuned, quantitative transcriptional response. In this talk, I will present how we can measure gene expression level as a function of tunable transcription factor activity and obtain the relationship termed the gene regulation function. Varying the interaction between transcription factors and DNA for a gene in budding yeast caused changes in the gene regulation function that are quantitatively consistent with a mechanistic model of gene expression. Dissection of the model reveals that nucleosomes are critical for a more highly evolvable gene regulation function.