Most mouse polyA⁺ erythro-megakaryocytic lncRNAs arise from conventional promoters and are regulated by key transcription factors. (A) Histone modifications H3K36me3, H3K4me1, and H3K4me3 were determined globally by ChIP-seq and analyzed at gene TSSs. Composite profiles are shown for promoter signatures (H3K4me3-high/H3K4me1-low) and enhancer signatures (H3K4me3-low/H3K4me1-high). The x-axis shows distance from TSS; y-axis shows average peak score for the indicated modifications. (B) Relative proportions of enhancer and promoter signatures at the TSSs of erythro-megakaryocytic coding and lncRNA genes. (C) Transcription factor (TF) occupancy at erythro-megakaryocytic coding and lncRNA genes measured by ChIP-seq. The genes are subclassified according to whether they are up- or downregulated in erythroblasts or megakaryocytes compared with MEPs, as measured by RNA-seq. (D) The expression of erythroid coding and noncoding genes in the Gata1^– mouse erythroblast line G1E-ER4 after activation of an estradiol-induced form of GATA1. (E) Model for megakaryocytic developmental priming. Genes with binding of a heptad of TFs in stem/progenitor cells are “primed” for megakaryocytic differentiation, and are activated during megakaryopoiesis and repressed during erythropoiesis. (F) Percentage of genes in each expression group showing occupancy by the TF heptad in the HPC-7 cell line. For both coding genes and lncRNAs, genes that are upregulated during megakaryopoiesis and either downregulated or unchanged during erythropoiesis show higher levels of genomic locus heptad occupancy in progenitor cells. Dn, downregulated; N, no change; Up, upregulated.