Novel Coregulators of Estrogen Receptor in Enhancer-regulated Transcription

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SUMMARY/ABSTRACT Novel Coregulators of Estrogen Receptor in Enhancer-regulated Transcription Estrogen (E2 or 17β-estradiol) and its nuclear receptor ERα play a critical role in the normal development and disease conditions of multiple organs, including the mammary glands, by binding mostly to distal enhancers. Increasing evidence suggests that functional dysregulation of ERα-bound enhancers can profoundly alter normal transcriptional programs, resulting in developmental defects, diseases, and hormone resistance. However, the molecular mechanisms underlying enhancer function/dysfunction are largely unknown. One of the main objectives of the parent grant, R01GM137009, is to understand how the cooperative interactions between YAP/TEAD and ERα control the context-specific function of ERα-bound enhancers in vivo through enhancer reprogramming. Specifically relevant to this supplement application, we aim to determine the functional attributes of YAP/TEAD in enhancer reprogramming during mammary gland development. To achieve this goal, we plan to dissect mammary glands from mouse models (YAP knockout and overexpression models) and isolate single cells for cell sorting or cellular phenotype analysis through flow cytometry. We are requesting equipment funding to purchase a single-cell dissociator combined with a user-friendly flow cytometer that will allow us to perform phenotype analysis of the mammary glands. This equipment is critical for my lab to complete this parental R01 project.