Fig. 4: CEBPA recruits NKX2-1 to promote the AT2 program and indirectly restricts the progenitor program.

A Heatmaps and profile plots of CEBPA and NKX2-1 binding for decreased and increased peak sets from Fig. 3F, as well as associated frequency distributions of CEBP, NKX, SOX motifs. CEBPA binds to decreased peaks but not increased peaks. NKX2-1 binding decreases (log2 fold change) for decreased peaks and increases (log2 fold change) for increased peaks in the mutant, corresponding to AT2 and progenitor/AT1-specific binding in wild type lungs. Diagram: a recruitment model, in which CEBPA normally recruits NKX2-1 to activate AT2 genes, whereas without CEBPA, NKX2-1 is released from AT2 genes and possibly relocates to progenitor and AT1 genes. Loss of NKX2-1 binding due to Cebpa deletion is associated with chromatin closure (open vs closed). See Supplementary Fig. 6A for nuclei sorting strategy. B Representative coverage plots of (A) showing a decreased peak near an AT2 gene Il33, and an increased peak near a progenitor gene Acaca. C Venn diagram showing NKX2-1 and CEBPA co-bound and single-bound peak sets in purified P2 AT2 cells (left) and frequency distributions of NKX and CEBP motifs for the co-bound peak set (right). D Heatmaps and profile plots for the 3 peak sets in (C) and associated log2 fold changes showing the largest decreases for the co-bound peak set.