Because TET2 and p300 played cooperative roles in maintaining the epigenome and enhancer landscape of HSPCs (26, 27), and our phenotypic data indicate that the loss of p300 in Tet2-deficient mice accelerated MDS progression, we next examined the TET2-independent function of p300 in HSPCs by comparing the epigenetic and gene expression profile of Tet2–/– HSPCs, before and after p300 loss. The gene discussed is EP300; the disease is myelodysplastic syndrome.