Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 388, Issue 10, pp 1009–1027

Cardiac gene expression data and in silico analysis provide novel insights into human and mouse taste receptor gene regulation

  • Simon R. Foster
  • Enzo R. Porrello
  • Maurizio Stefani
  • Nicola J. Smith
  • Peter Molenaar
  • Cristobal G. dos Remedios
  • Walter G. Thomas
  • Mirana Ramialison
Original Article

DOI: 10.1007/s00210-015-1118-1

Cite this article as:
Foster, S.R., Porrello, E.R., Stefani, M. et al. Naunyn-Schmiedeberg's Arch Pharmacol (2015) 388: 1009. doi:10.1007/s00210-015-1118-1

Abstract

G protein-coupled receptors are the principal mediators of the sweet, umami, bitter, and fat taste qualities in mammals. Intriguingly, the taste receptors are also expressed outside of the oral cavity, including in the gut, airways, brain, and heart, where they have additional functions and contribute to disease. However, there is little known about the mechanisms governing the transcriptional regulation of taste receptor genes. Following our recent delineation of taste receptors in the heart, we investigated the genomic loci encoding for taste receptors to gain insight into the regulatory mechanisms that drive their expression in the heart. Gene expression analyses of healthy and diseased human and mouse hearts showed coordinated expression for a subset of chromosomally clustered taste receptors. This chromosomal clustering mirrored the cardiac expression profile, suggesting that a common gene regulatory block may control the taste receptor locus. We identified unique domains with strong regulatory potential in the vicinity of taste receptor genes. We also performed de novo motif enrichment in the proximal promoter regions and found several overrepresented DNA motifs in cardiac taste receptor gene promoters corresponding to ubiquitous and cardiac-specific transcription factor binding sites. Thus, combining cardiac gene expression data with bioinformatic analyses, this study has provided insights into the noncoding regulatory landscape for taste GPCRs. These findings also have broader relevance for the study of taste GPCRs outside of the classical gustatory system, where understanding the mechanisms controlling the expression of these receptors may have implications for future therapeutic development.

Keywords

Taste receptor Heart De novo motif discovery Cis-regulatory modules Transcription factor 

Abbreviations

bHLH

Basic helix-loop-helix

bZIP

Basic leucine zipper

ChIP

Chromatin immunoprecipitation

ENCODE

Encyclopedia of DNA elements

GPCRs

G protein-coupled receptors

I/R

Ischemia/reperfusion

LAD

Left anterior descending

LV

Left ventricular

PWM

Position weight matrix

TAS1R/T1R

Taste receptor type 1

TAS2R/T2R

Taste receptor type 2

TFBS

Transcription factor binding sites

Supplementary material

210_2015_1118_MOESM1_ESM.docx (1.3 mb)
ESM 1(DOCX 1281 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Simon R. Foster
    • 1
  • Enzo R. Porrello
    • 1
  • Maurizio Stefani
    • 2
  • Nicola J. Smith
    • 3
  • Peter Molenaar
    • 4
    • 5
  • Cristobal G. dos Remedios
    • 2
  • Walter G. Thomas
    • 1
  • Mirana Ramialison
    • 6
  1. 1.School of Biomedical SciencesThe University of QueenslandBrisbaneAustralia
  2. 2.Muscle Research Unit, Department of Anatomy, Bosch InstituteThe University of SydneySydneyAustralia
  3. 3.Victor Chang Cardiac Research Institute, Darlinghurst, Australia, Faculty of MedicineThe University of New South WalesSydneyAustralia
  4. 4.School of Biomedical SciencesQueensland University of TechnologyBrisbaneAustralia
  5. 5.School of MedicineThe University of QueenslandBrisbaneAustralia
  6. 6.Australian Regenerative Medicine InstituteMonash UniversityClaytonAustralia