This significantly reduced chromatin looping between the BRRIAR locus and BHLHE40 promoter (Fig. 2e and Supplementary Fig. 2b), accompanied by decreased BHLHE40 expression, suggesting BRRIAR regulates BHLHE40 in ER + breast cancer cells (Fig. 2f and Supplementary Fig. 2c). This evidence concerns the gene ESR1 and breast carcinoma.