A hypothetical model illustrates that the gradual decrease in PERP and ERBB3 transcript levels along the EMT spectrum potentially correlates with the selective loss of RAD21 and GRHL2-mediated DNA looping structures. In an epithelial cell state, GRHL2 associates with RAD21 possibly to mediate intact chromatin loop structures bringing proximal and distal regulatory elements into the ERBB3 (top) and PERP (bottom) loci, and these structures might render abundant transcriptions. In the intermediate E/M-like cell state, the selective loss of RAD21/GRHL2 enrichment in the P12 amplicon region of the PERP loci potentially leads to the dissociation of proximal loop structures. There is no significant change in the ERBB3 loci. However, as these cells transit into a mesenchymal cell state, the loss of GRHL2 expression might lead to the distortion of cohesin structures connecting proximal and distal regulatory elements, which may result in the reduced transcriptional activity. Illustration created with Biorender.com.