Molecular and cellular studies on transcriptional regulation of neurogranin

Abstract

<P>IN THIS STUDY, THE BASAL TRANSCRIPTIONAL ACTIVITY OF 5A??-FLANKING REGION OF THE MOUSE NEUROGRANIN (NG) GENE WAS INVESTIGATED IN SEVERAL CELL LINES. RESULTS SHOWED THAT A 258 BP 5A??-FLANKING SEQUENCE PROXIMAL TO TRANSCRIPTIONAL START SITE (TSS) OF NG GENE CONFERS THE BASAL PROMOTER ACTIVITY. A GC-BOX WAS REVEALED TO PLAY A CRITICAL ROLE IN PROVIDING BASAL LEVEL PROMOTER ACITIVITY. OVEREXPRESSION OF SP1 TRANSACTIVATES THE PROMOTER ACITIVITY WHILE ECTOPIC EXPRESSION OF SP3 REDUCES THE TRANSCRIPTIONAL ACTIVITY OF 5A??-FLANKING SEQUENCE OF NG GENE. UNEXPECTEDLY, THESE TWO SP FAMILY TRANSCRIPTIONAL FACTORS DID NOT FORM ANY PROTEIN-DNA COMPLEX WITH GC-BOX, WHICH WAS DEMONSTRATED BY MOBILITY SHIFT ASSAY.</P><P>MEANWHILE A BIPHASIC EFFECT OF NO ON TRANSCRIPTIONAL REGULATION OF NG GENE DEPENDING ON THE CONCENTRATION OF NO WAS SUGGESTED IN THE STUDY. AT PHYSIOLOGICAL CONCENTRATIONS, NO UPREGULATES THE TRANSCRIPTION OF NG GENE THROUGH NO-GUANYLYL CYCLASE(GC)-CGMP PATHWAY. AT PATHOPHYSIOLOGICA