Impact of the 3D Chromatin Organization on Promoter-Super-Enhancer Interactions in Embryonic Stem Cells and Cancer Cells

The interaction of enhancers and super-enhancers (SE) with promoters is functionally significant for the regulation of gene expression. The pattern of these interactions plays a key role in various processes, such as differentiation, malignant transformation, etc. In order to quantify the relationship between 3D chromatin organization and promoter-SE contacts, a computational analysis of chromatin conformations near the murine Nanog pluripotency gene is performed for embryonic stem cells (mESC) and lymphoma (CH12LX) cells. Using the polymer modeling approach, the following parameters of the promoter-SE interactions are identified: the distribution of distances between the Nanog promoter and the SEs, and the frequency of contacts with one and several SEs simultaneously. Polymer modeling reveals that in normal mESC expressing Nanog, the frequency of the contacts of promoters with SEs is higher than in cancer cells, and complex contacts with two or more SEs are more frequent. Numerical results indicate the existence of a small subpopulation of cancer cells, where the promoter contacts simultaneously three SEs. The predicted subpopulation of cancer cells with multiple promoter-SE contacts may be predisposed to increased stemness and hypothetically be considered as a reservoir for the appearance of cancer stem cells.

Automated summary

The interaction between enhancers and super-enhancers with promoters plays a crucial role in gene expression regulation. Computational analysis of chromatin conformations near the Nanog pluripotency gene in embryonic stem cells and lymphoma cells reveals differences in the frequency and complexity of contacts between promoters and super-enhancers. Numerical results indicate the existence of a subpopulation of cancer cells with multiple promoter-super-enhancer contacts, suggesting a potential link to increased stemness and the development of cancer stem cells.