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. Author manuscript; available in PMC: 2023 Feb 1.
Published in final edited form as: Curr Opin Genet Dev. 2021 Nov 19;72:45–52. doi: 10.1016/j.gde.2021.10.004

Figure 2. Distal regulation of gene activity in the context of heterogeneity in TAD structure:

Figure 2

A gene may experience various types of interactions with enhancers leading to a gradient of gene activation. (A) Enhancers from a neighboring TAD infrequently interact with a gene resulting in weak transcriptional activation. (B) Stochastic variations in the TAD boundary or a deletion of boundary element can transiently extrude enhancers from adjoining TADs into a single TAD to transiently increase the activation from such enhancers. (C) When TAD boundaries are stable, an enhancer within the same TAD interacts frequently with the gene and strongly upregulates its expression. (D) Simultaneous interaction with enhancers on both same and adjacent TADs can additively contribute to gene activation that is modulated by variation in TAD structure (D and E).