Sustained hypertension‐induced dynamic transcriptional regulation in the nucleus tractus solitarius

Abstract

In this study, we focus on the transcriptional regulation mediated by the factors AP‐1 and CREB in the adaptive response of the nucleus tractus solitarius (NTS) to sustained hypertension. Analysis of a gene expression time series data revealed extensive differential regulation in NTS in response to elevation of systemic blood pressure. We have pursued a bioinformatics approach to analyze the upstream promoter sequences of these differentially regulated genes for the presence of AP‐1 and CREB binding sites. Our analysis resulted in a total of 500 differentially regulated genes. We have experimentally validated a focused subset of neuronal function relevant genes (e.g., ion channels and signaling kinases) through a novel Fast Carrier Chromatin Immunoprecipitation approach. Our results reveal dynamic changes in binding of AP‐1 and CREB at these promoters, specifically phospho‐CREB binding at the c‐fos and Tyrosine Hydroxylase (TH), and AP‐1 binding at the TH and Angiotensin II receptor, type 1 gene promoters. These results indicate the combinatorial regulation by AP‐1 and CREB in shaping the neural adaptation in NTS in response to elevated blood pressure. Research Support: NIH/HLB R33 HL087361 to JSS.