Figure 8 | Scientific Reports

Figure 8

From: Chronic stress and intestinal barrier dysfunction: Glucocorticoid receptor and transcription repressor HES1 regulate tight junction protein Claudin-1 promoter

Figure 8

Proposed model for regulatory circuits of HES1-CLDN1 along colon crypt axis. Regulatory circuits of HES1-CLDN1 pathways are similar to that of colon & neuroectoderm patterning Notch–Delta inhibitor-activator pair. Potential chromosomal intra-communication between HES1 and CLDN1 coded close and oppositely on human chromosome 3 made them candidates to test Alan Turing’s 1952 gene morphogen hypothesis. Glucocorticoid activated NR3C1 inhibits HES1 promoter and activate CLDN1 promoter via GRE elements. Chronically elevated glucocorticoid levels may impair colon epithelium barrier function via HES1-NR3C1 axis. This model is consistent with an activator/inhibitor gene morphogen pair, originally proposed by Alan Turing23, 26 (refer to Discussion Section for additional information).

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