Identification of Nrg1 enhancer binding proteins

Hyperglycemia is a risk factor for breast cancer-related morbidity and mortality. Hyperglycemia induces Neuregulin 1 (Nrg1) overexpression in breast cancer, which subsequently promotes tumor progression. However, molecular mechanisms underlying hyperglycemia-induced Nrg1 overexpression remain poorly understood. Here, We used DNA-protein pull-down using Nrg1 enhancer sequence as bait followed by LC/MS and identified RBPJ as a key component of the Nrg1 enhanceosome. We show that hyperglycemia causes active histone modifications at the Nrg1 enhancer, forming enhanceosome complexes where RBPJ, P300, and SETD1A are recruited to upregulate Nrg1 expression.