ENAGenomicsDaiichi Sankyo Co., Ltd.https://www.ebi.ac.uk/ena/browser/view/PRJNA1127050Polycomb repressive complex 2 (PRC2) represses transcription by trimethylation of histone H3 at lysine 27. Valemetostat is a potent inhibitor of enhancer of zeste homolog (EZH)2 and EZH1, which are histone methyltransferases of PRC2. PRC2 inhibitors, including valemetostat, have been showing promises in multiple cancer types. PRC2 inhibitors, however, can induce thrombocytopenia as a class adverse effect. To better understand valemetostat-induced thrombocytopenia, we performed single-cell ATAC-seq and bulk RNA-seq for human bone marrow CD34+ cells that were in vitro differentiated into megakaryocytes.ENAfalseThe EZH2 and EZH1 inhibitor valemetostat derepresses p16INK4a to induce early endomitotic exit in megakaryocytes2025-07-042025-07-04PRJNA1127050