Figure 4: PITX1 co-operates with SOX2 and TRP63 to control tumor propagating SCC cell defining gene regulatory elements.
(A) Transcription factor motifs surrounding PITX1 bound cis-regulatory elements. (B) Endogenous PITX1 immuno-precipitates TRP63 and SOX2, but not KLF4 or Vinculin (VIN). (C) Confocal micrographs identify PITX1 in basal and KLF4 in supra-basal SCC cells. (D) K-Means cluster analyses of ChIP-seq peaks centered on the union of PITX1, SOX2, TRP63, and KLF4 motif containing ChIP-seq peaks (left panel). Boxes right to the heat maps indicate the number of peaks present in each cluster. GO and PANTHER enrichment analyses by GREAT. (E) Venn diagram illustrates PITX1-SOX2-TRP63 bound genes in mouse and human TPCs. Genes repressed by PITX1 are red and activated ones are blue. (F) Working model for the regulation of TPC renewal and differentiation by a bi-stable transcriptional network. See also Figure S4 and S5 and Table S3–S5.