February 18 , 2009
3 pm in Howey Physics Room N110

 

Harold D. Kim
Depts. of Molecular and Cellular Biology, and Chemistry and Chemical Biology
Harvard University

"How the packaging of DNA influences gene expression"

 

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.