We are interested in studying the control of gene expression. Differences in gene expression underlie the tremendous variety of cell types in our bodies and account for most of the innate differences between you and me or between me and chimpanzee. Differences in gene expression are encoded in the non-transcribed parts of our genome called cis regulatory elements. These regions bind proteins (in a sequence dependent manner) that affected the transcription of surrounding genes. Surprisingly, these regulatory elements can be very far away (in linear-sequence) from the transcribed elements they control, they are frequently tens to hundreds of thousands of basepairs apart. We are interested in understanding how such long-range interactions occur, how they achieve target specificity, and how they may be reprogrammed by alterations to the genome sequence.
We believe the answers to these questions require understanding the 3D organization of the genome. While interactions between regulatory elements and transcribed elements are long-range, they still occur only in cis (on the same chromosome) and are not known beyond the scale of a couple megabases. This is one line of evidence suggesting physical proximity of the elements is necessary for regulatory interaction. Moreover if one regulatory element is artificially inserted immediately next to a transcribed element that it does not normally regulate, it will generally start to modify transcription, indicating that physical proximity is generally sufficient for regulatory interaction. Nonetheless, it is not well understood how the genome is organized in the 3D environment of the nucleus to promote the correct interactions and avoid potentially deleterious ones or what mechanisms regulate this organization.