ADB2021

Michael Larcombe

Polo Lab

Dissecting The Regulatory Complexes Controlling Expression Of The Pluripotency Factors

Cellular identity is ultimately dictated by the interaction of transcription factors with regulatory elements (REs) to control gene expression. Genome-wide epigenome profiling techniques have significantly increased our understanding of cell-specific utilization of REs. However, it remains difficult to dissect the majority of factors interacting with these REs due to the lack of appropriate techniques. We developed TINC: TALE-mediated isolation of nuclear chromatin to dissect the factors responsible for cell-specific utilization of a RE. Using TINC we interrogated the protein complex formed at the Nanog promoter in embryonic stem cells, identifying known and novel complex members. To address the major limitations of single-locus proteomics technologies such as TINC, I’m currently optimizing tandem immunoprecipitation strategies to reduce non-specific enrichment of proteins.