PML::RARA and GATA2 proteins interact via DNA templates to induce aberrant self-renewal in mouse and human hematopoietic cells

This study used ChIP-seq, CUT&RUN, RNA-seq, single-cell RNA-seq (scRNA-seq), and ATAC-seq to identify the genomic binding sites of PML::RARA and GATA2 in primary hematopoietic stem and progenitor cells (HSPCs), as well as the epigenetic and transcriptional changes associated with those binding sites. To identify the genomic binding sites, PML::RARA and Gata2 were fused to a V5 epitope tag and expressed in HSPCs using murine stem cell virus (MSCV) based vectors, followed by anti-V5 ChIP-seq and CUT&RUN. A V5-tagged C88A mutant in the RARA domain of PML::RARA, which ablates binding to DNA, was used as a negative control.