Cancer Institute Seminar Series - Dr Maša Roller

Hosted by Dr Javier Herrero

My research focuses on regulatory evolution through retrotransposons, mobile genetic elements that can insert copies of themselves in the genome. A number of retrotransposons are known to have regulatory activity, but the extent to which they contribute to reshaping mammalian regulomes is not well understood. I focused on the evolution of promoters, enhancers, and CCCTC-binding factor (CTCF), whose genomic position can be mapped genome-wide using chromatin immunoprecipitation followed by genome sequencing (ChIP-seq) with specific antibodies.

To explore tissue-specific evolution of mammalian regulatory regions, we mapped active promoters and enhancers in four tissues of ten mammalian species using ChIP-seq experiments for specific histone modifications and matched RNA-seq assays. We compared the evolutionary turnover of tissue-specific and tissue-shared regulatory regions and found that tissue-specific regulatory regions evolve more rapidly than their tissue-shared counterparts. Furthermore, we found that tissue-specific and tissue-shared regulatory regions preferentially associate with different transposable elements. Tissue-specific regions associate with the younger LINE L1s, while tissue-shared regions associate with older LINE L2s, indicating a more recent evolution of tissue-specific functions. To elucidate the mechanisms which balance between lineage-specific transposon-associated regulatory evolution and maintaining conserved function, we used a model of closely related mouse species. By profiling the activity of CTCF binding genome-wide through ChIP-seq experiments, we were able to describe the microevolutionary trends of retrotransposon-associated transcription factor binding evolution.

We found species-specific CTCF binding expansion in an evolutionary young transposable element, with a single nucleotide change in the binding site for CTCF. We also explored CTCF evolution at the boundaries of transcriptionally active domains (TADs), basic 3D genome structures thought to be largely invariant between species. We found that TAD boundaries abound with dynamic species-specific CTCF binding site insertions. These species-specific sites cluster together with conserved sites, to bind cohesin and maintain TAD boundaries. My research is starting to unravel the extent and mechanisms through which transposable elements contribute to regulatory evolution in mammals

• Dr Masa Roller academic profile

This seminar has been sponsored in part by the Biomedical Research Centre and Cancer Research UK