Volume 9 Supplement 1
Transcriptional regulation network analysis of the hypertension-perturbed nucleus tractus solitarius
© Gonye et al; licensee BioMed Central Ltd. 2008
Published: 11 July 2008
Neurons expressing the angiotensin II (angII) AT1 receptor (AT1R) in the nucleus tractus solitarius (NTS) have been implicated in many of the functions assigned to angII in the CNS including roles in neural control of cardiovascular function, in particular blood pressure regulation, the baroreflex, stress responses and maintenance of homeostasis (thirst and salt appetite). AngII, acting through the AT1 receptor has two main effects on neurons: a rapid and transient modulation of K+ and Ca2+ currents and longer lasting changes in gene expression, ultimately leading to modulation of noradrenergic neuronal networks regulating cardiovascular function . Using a combined experimental and computational systems level analysis, we have investigated the transcriptional regulatory network downstream of AT1R activation by using N1E-115 neuroblastoma cells engineered to express AT1Rs as a model system and have recently extended this to the NTS.
We have applied transcriptional regulatory network analysis (TRNA), using our bioinformatics framework, Promoter Analysis and Interaction Network Toolset (PAINT)  to the response of the NTS both directly to angII and to phenylephrine-induced acute hypertension. TRNA makes the fundamental assumption that many co-expressed genes share transcription regulatory elements (TRE's), typically transcription factor binding sites, in their promoters, leading to co-regulation. This results in a higher frequency of the suspect binding sites in the promoters of sets of co-regulated genes relative to randomly associated sets of genes. PAINT uses bioinformatics in combination with robust statistical approaches to identify those regulatory elements significantly enriched in the promoters of the genes of interest relative to random gene sets. Predicted TF:promoter interactions are tested using chromatin immunoprecipitation PCR (ChIP-PCR) with chromatin from untreated and perturbed (angII or hypertension) NTS or cell lines.
Results and conclusions
TRNA of AT1R-dependent NTS Expression
The authors wish to acknowledge the expert technical assistance of H. Liu, Y. Liu and M. Payne in support of these studies and the intellectual input of the other members of the Daniel Baugh Institute for Functional Genomics and Computational Biology. This work was supported by grants from the NIGMS and NHLBI (J. Schwaber, PI).
- Phillips MI, Sumners C: Angiotensin II in central nervous system physiology. Regul Pept. 1998, 78 (1–3): 1-11. 10.1016/S0167-0115(98)00122-0.View ArticlePubMedGoogle Scholar
- Vadigepalli R, Chakravarthula P, Zak DE, Schwaber JS, Gonye GE: PAINT: a promoter analysis and interaction network generation tool for gene regulatory network identification. Omics. 2003, 7 (3): 235-252. 10.1089/153623103322452378.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd.