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. Author manuscript; available in PMC: 2022 Jul 10.
Published in final edited form as: Mol Psychiatry. 2022 Jan 10;27(3):1599–1610. doi: 10.1038/s41380-021-01390-w

Figure 5. EGR3 drives gene expression via binding sites in the Htr2a promoter and EGR3 and HTR2A expression is reduced in schizophrenia brains.

Figure 5.

(A-C) Schematics of dual luciferase/SEAP reporter constructs containing EGR consensus binding sites and results of in vitro assays in neuro2a cells. CMV-driven EGR3 overexpression significantly upregulates expression of luciferase reporters driven by (A) Arc promoter (t4 = 42.28; p < 0.0001), (B) Htr2aD distal promoter (t4 = 21.17; p < 0.0001), and (C) Htr2aP proximal promoter (t4 = 8.977, p = 0.0009) regions. (D) Western blot validation of EGR3 expression following transfection with CMV-EGR3 versus CVM empty vector, from cultures expressing reporter constructs driven by promoters from Arc, Htr2aD, Htr2aP, or negative promoter control vector. Unpaired student’s t-test, (A-D) n = 3 per group. (E, F) EGR3 and HTR2A mRNA levels are significantly decreased in human brain tissue samples from the prefrontal cortex of schizophrenia patients compared to controls. Microarray (Robust Multi-Array Average) gene expression data derived from NCBI Geo database GSE53987 showing significant decrease in (E) EGR3 (U = 81, p = 0.0331) expression and (F) HTR2A (U = 63, p = 0.0050) expression, in control (n = 19) vs. schizophrenia (n = 15) patients. Mann-Whitney U test, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. Values represent means ± SEM. (Abbreviations: CMV - cytomegalovirus, GLuc - Gaussia luciferase, SEAP - secreted alkaline phosphatase).