Investigating the effects of chromatin architecture on gene regulation

Transcription factors (TFs) are proteins that bind to specific sites on DNA, where they control the activity of genes. Despite the good success of current models to predict TF binding profiles, there are cases where all models fail. One frequent aspect of these models is that the DNA is linear, but this is clearly not the case and recent studies showed that the DNA in eukaryotes is highly compacted.

We plan to investigate whether the 3D structure of chromatin influences the binding of TFs and we will assess whether changes in the binding profiles of TF are specific to loci where the 3D structure of the DNA is changed. We will also look at whether DNA accessibility also changes at these loci (to evaluate whether DNA accessibility mediates this interaction). We will also investigate whether these changes in TF binding translate into changes in transcription levels. We will study Drosophila cells to generate binding profiles and expression data for the suppressor of hairless protein.