biostudies-literatureAdhikary SNCI NIH HHS1398https://www.ebi.ac.uk/biostudies/studies/S-EPMC6438984biostudies-literatureUnknown10(1)The roles of Plant Homeodomain (PHD) fingers in catalysis of histone modifications are unknown. We demonstrated that the PHD finger of Ubiquitin Protein Ligase E3 Component N-Recognin7 (UBR7) harbors E3 ubiquitin ligase activity toward monoubiquitination of histone H2B at lysine120 (H2BK120Ub). Purified PHD finger or full-length UBR7 monoubiquitinated H2BK120 in vitro, and loss of UBR7 drastically reduced H2BK120Ub genome-wide binding sites in MCF10A cells. Low UBR7 expression was correlated with occurrence of triple-negative breast cancer and metastatic tumors. Consistently, UBR7 knockdown enhanced the invasiveness, induced epithelial-to-mesenchymal transition and promoted metastasis. Conversely, ectopic expression of UBR7 restored these cellular phenotypes and reduced tumor growth. MechaNature communicationsAtypical plant homeodomain of UBR7 functions as an H2BK120Ub ligase and breast tumor suppressor.PMC6438984P30 CA016672R00 CA160578K99 CA160578Sengupta ISrivastava DKRaman ATYang FTarco ESahin AATapia CRai KDas CMaitituoheti MTerranova CAdhikary SRoy SDasgupta AMa JBassett RChakravarti DfalseAtypical plant homeodomain of UBR7 functions as an H2BK120Ub ligase and breast tumor suppressor.The roles of Plant Homeodomain (PHD) fingers in catalysis of histone modifications are unknown. We demonstrated that the PHD finger of Ubiquitin Protein Ligase E3 Component N-Recognin7 (UBR7) harbors E3 ubiquitin ligase activity toward monoubiquitination of histone H2B at lysine120 (H2BK120Ub). Purified PHD finger or full-length UBR7 monoubiquitinated H2BK120 in vitro, and loss of UBR7 drastically reduced H2BK120Ub genome-wide binding sites in MCF10A cells. Low UBR7 expression was correlated with occurrence of triple-negative breast cancer and metastatic tumors. Consistently, UBR7 knockdown enhanced the invasiveness, induced epithelial-to-mesenchymal transition and promoted metastasis. Conversely, ectopic expression of UBR7 restored these cellular phenotypes and reduced tumor growth. Mecha2019-01-01T00:00:00Z2019 Mar2026-05-03T16:42:14.847Z2019-06-06T21:03:41ZS-EPMC64389843092331510.1038/s41467-019-08986-5