{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327307/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327307"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"DOT1L shapes ncPRC1-target gene repression to maintain cell identity of DLBCL [RNA-Seq]","description":"Germinal center (GC) B cell-like diffuse large B cell lymphoma (GCB-DLBCL) depends on the cooperative activity of the histone methyltransferases DOT1L and EZH2 to maintain its pro-proliferative GCB cell identity while repressing plasma cell (PC) differentiation. To explore the mechanisms underlying the co-dependency between DOT1L and EZH2 in GCB-DLBCL, we performed an EZH2 inhibition (EZH2i)-anchored genome-wide CRISPR interference screen and identified multiple candidate genes encoding components of non-canonical (nc) PRC1 complexes, including USP7, KDM2B, RING1, and PCGF1. We identified USP7 as potential direct target of DOT1L, whose downregulation was associated with increased EZH2i sensitivity in multiple GCB-DLBCL cell lines. Furthermore, we observed that DOT1L influences the composition of chromatin-bound ncPRC1 complexes and regulates, in part, the deposition of H2AK119 monoubiquitination (H2AK119ub1) at gene promoters co-occupied by H3K27me3, here defined as PRC1/2 target genes. These PRC1/2 targets were specifically enriched in PC signature genes, whose derepression was associated with DOT1L inhibition (DOT1Li)-mediated loss of H2AK119ub1. This study reveals novel insights into the role of DOT1L and its functional co-dependence with EZH2 in maintaining GCB identity in DLBCL, supporting a model in which concurrent reduction of H2AK119ub1 and H3K27me3 promotes differentiation toward an anti-proliferative, plasma cell–like state.","dates":{"publication":"2026/06/19"},"accession":"GSE327307","cross_references":{"GSM":["GSM9653220","GSM9653221","GSM9653210","GSM9653211","GSM9653222","GSM9653223","GSM9653212","GSM9653217","GSM9653206","GSM9653218","GSM9653207","GSM9653208","GSM9653219","GSM9653209","GSM9653224","GSM9653213","GSM9653214","GSM9653203","GSM9653225","GSM9653226","GSM9653215","GSM9653204","GSM9653205","GSM9653216"],"GPL":["24676"],"GSE":["327307"],"taxon":["Homo sapiens"]}}