This hypothesis has been further supported by studies investigating the function of RNF20 and RNF4013–17, while we and others have uncovered tumor-supportive roles of RNF20 and RNF40 in colorectal cancer18,19 and androgen-dependent prostate cancer20, suggesting that RNF20/RNF40-driven H2B monoubiquitination plays a context-dependent role in cancer. Here, H2BC21 is linked to cancer.