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. Author manuscript; available in PMC: 2014 Dec 1.

Published in final edited form as: J Neurochem. 2013 Jul 19;127(6):10.1111/jnc.12346. doi: 10.1111/jnc.12346

Results are shown as mean ± SEM. Significant differences (P <0.05) are bold.

(a) Protein trafficking into the regulated secretory pathway in PC12 cells, co-transfected with pCMV-SGCD and pCMV-CHGA-EAP chimera. Decreased stimulated secretion of Chromogranin A (CHGA) following SGCD exposure in PC12 cells, with and without secretory stimulation. In this system, co-expression of SGCD enhances CHGA secretory protein sorting to the regulated pathway.

(b) Transcription factor binding. The peak associated SGCD variant disrupts a potential Hepatocyte nuclear factor 3-beta (HNF3B; aka Forkhead box protein A2 (FOXA2)) transcriptional motif. The SGCD transcriptional motif is shown to maintain conservation through inter-species sequence homology; polymorphism in bold, SGCD promoter SNP rs1835919 ([-] strand, as T>C). Also displayed is the graphical representation of HNF3B motif multiple sequence alignment and the position frequency and weight matrix representing known variation at the HNF3B alignment.

(c) Chromatin Conformation Capture. The plot indicates that the local interaction domain <http://chromosome.sdsc.edu> accessible to the rs1835919 region includes the entire SGCD gene, in both the longer (uc0031wa.1) or RefSeq (NM_000337) versions.

(d) The schematic presents a hypothetical framework integrating the overall rationale and experimental results of our study, and suggests future questions for exploration. CHGB indicates chromogranin B; all other abbreviations as in Figures 1 and 3. Ba²⁺ indicates barium; EAP, embryonic alkaline phosphatase.

Results are shown as mean ± SEM. Significant differences (P <0.05) are bold.

(a) Protein trafficking into the regulated secretory pathway in PC12 cells, co-transfected with pCMV-SGCD and pCMV-CHGA-EAP chimera. Decreased stimulated secretion of Chromogranin A (CHGA) following SGCD exposure in PC12 cells, with and without secretory stimulation. In this system, co-expression of SGCD enhances CHGA secretory protein sorting to the regulated pathway.

(b) Transcription factor binding. The peak associated SGCD variant disrupts a potential Hepatocyte nuclear factor 3-beta (HNF3B; aka Forkhead box protein A2 (FOXA2)) transcriptional motif. The SGCD transcriptional motif is shown to maintain conservation through inter-species sequence homology; polymorphism in bold, SGCD promoter SNP rs1835919 ([-] strand, as T>C). Also displayed is the graphical representation of HNF3B motif multiple sequence alignment and the position frequency and weight matrix representing known variation at the HNF3B alignment.

(c) Chromatin Conformation Capture. The plot indicates that the local interaction domain <http://chromosome.sdsc.edu> accessible to the rs1835919 region includes the entire SGCD gene, in both the longer (uc0031wa.1) or RefSeq (NM_000337) versions.

(d) The schematic presents a hypothetical framework integrating the overall rationale and experimental results of our study, and suggests future questions for exploration. CHGB indicates chromogranin B; all other abbreviations as in Figures 1 and 3. Ba²⁺ indicates barium; EAP, embryonic alkaline phosphatase.