title: Tissue-specific gene expression and regulation in liver and muscle following chronic corticosteroid administration.
abstract: Although corticosteroids (CSs) affect gene expression in multiple tissues, the array of genes that are regulated by these catabolic steroids is diverse, highly tissue specific, and depends on their functions in the tissue. Liver has many important functions in performing and regulating diverse metabolic processes. Muscle, in addition to its mechanical role, is critical in maintaining systemic energy homeostasis and accounts for about 80% of insulin-directed glucose disposal. Consequently, a better understanding of CS pharmacogenomic effects in these tissues would provide valuable information regarding the tissue-specificity of transcriptional dynamics, and would provide insights into the underlying molecular mechanisms of action for both beneficial and detrimental effects. We performed an integrated analysis of transcriptional data from liver and muscle in response to methylprednisolone (MPL) infusion, which included clustering and functional annotation of clustered gene groups, promoter extraction and putative transcription factor (TF) identification, and finally, regulatory closeness (RC) identification. This analysis allowed the identification of critical transcriptional responses and CS-responsive functions in liver and muscle during chronic MPL administration, the prediction of putative transcriptional regulators relevant to transcriptional responses of CS-affected genes which are also potential secondary bio-signals altering expression levels of target-genes, and the exploration of the tissue-specificity and biological significance of gene expression patterns, CS-responsive functions, and transcriptional regulation. The analysis provided an integrated description of the genomic and functional effects of chronic MPL infusion in liver and muscle.
authors.affiliation: BioMaPS Institute for Quantitative Biology, Rutgers University, Piscataway, NJ, USA.
authors.forename: Tung T
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY, USA. ; Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA. ; New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Almon
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY, USA. ; Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Debra C
authors.initials: DC
authors.lastname: Dubois
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Sukumaran
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA. ; New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jusko
authors.affiliation: Biomedical Engineering Department, Rutgers University, Piscataway, NJ, USA. ; Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ, USA.
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Androulakis
keywords: corticosteroids; gene expression; gene regulation; glucocorticoids; liver; muscle; promoter analysis