Prdm16s activates myeloid transcription factors by acting on super enhancers. (A) Overlaps in H3K4me3 and H3K27ac peaks between MEPs and L-MEPs (n = 3). (B) Genomic snapshot at the Spi1 and Elf1 loci showing H3K27ac and H3K4me3 chromatin immunoprecipitation followed by sequencing (ChIP-seq) in normal MEPs and L-MEPs (n = 3), Prdm16s CUT&RUN (C&R) in L-MEPs (n = 2), and promoter capture Hi-C data as shown by red arches. Peaks that are statistically different (P < 10⁻⁹⁷) between L-MEPs and MEPs are indicated by green bars; y-axis represents counts per million reads. (C) Overlap in super enhancers between normal MEPs and L-MEPs (n = 3). (D) Distribution of H3K27ac density as determined by ChIP-seq data across super enhancers in L-MEPs (n = 3). (E) Distribution of Prdm16s C&R peaks in annotated regions of the genome (n = 2). (F) Motif analysis of Prdm16s binding sites identified by C&R revealed enrichment of motifs of myeloid transcription factors and CTCF. (G-H) Overlap between super enhancers (G) and typical enhancers (H) with Prdm16s binding site in L-MEPs. ncRNA, noncoding RNA; TSS, transcription start site; WT, wild type; UTR, untranslated region.