Quite a few studies revealed several transcriptional factors could be recruited to ERɑ promoter regions, such as SP1, AP‐1 and CBP.27, 28, 29 But, recent papers also indicate the important role of histone modification proteins in regulation ERɑ expression.30 For example, the histone deacetylase inhibition could rescue ERɑ expression even in ERɑ‐negative breast cancer cells.31 In our study, we observed a novel histone modification protein‐RNF168, which modulates ERɑ signalling via direct binding to ERɑ gene promoter regions. The gene discussed is SP1; the disease is breast cancer.