Need Help?


Gene Regulation and Systems Biology

251,079 Journal Article Views | Journal Analytics

Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts

Submit a Paper

Publication Date: 12 Jul 2011

Type: Original Research

Journal: Gene Regulation and Systems Biology

Citation: Gene Regulation and Systems Biology 2011:5 41-59

doi: 10.4137/GRSB.S7457


Background: To identify in vivo new cardiac binding sites of serum response factor (SRF) in genes and to study the response of these genes to mild over-expression of SRF, we employed a cardiac-specific, transgenic mouse model, with mild over-expression of SRF (Mild-O SRF Tg). Methodology: Microarray experiments were performed on hearts of Mild-O-SRF Tg at 6 months of age. We identified 207 genes that are important for cardiac function that were differentially expressed in vivo. Among them the promoter region of 192 genes had SRF binding motifs, the classic CArG or CArG-like (CArG-L) elements. Fifty-one of the 56 genes with classic SRF binding sites had not been previously reported. These SRF-modulated genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes was significantly increased. Using public databases of mouse models of hemodynamic stress (GEO database), we also found that similar altered expression of the SRF-modulated genes occurred in these hearts with cardiac ischemia or aortic constriction as well. Conclusion and significance: SRF-modulated genes are actively regulated under various physiological and pathological conditions. We have discovered that a large number of cardiac genes have classic SRF binding sites and were significantly modulated in the Mild-O-SRF Tg mouse hearts. Hence, the mild elevation of SRF protein in the heart that is observed during typical adult aging may have a major impact on many SRF-modulated genes, thereby affecting cardiac structure and performance. The results from our study could help to enhance our understanding of SRF regulation of cellular processes in the aged heart.




Supplementary Files 1  (127.67 KB PDF FORMAT)

BibTex citation   (BIBDESK, LATEX)




What Your Colleagues Say About Gene Regulation and Systems Biology
Publishing in Gene Regulation and Systems Biology was a very positive experience.  I was impressed by the fast and uncomplicated submission process as well as the clear and professional peer review process which helped to improve the manuscript.  The Libertas Academica team was very patient and helpful.  I would definitely recommend the journal to other colleagues in the field!
Dr Cameron Moshfegh (Federal Institute of Technology, Switzerland)
More Testimonials

Quick Links

New article and journal news notification services
Email Alerts RSS Feeds
Facebook Google+ Twitter
Pinterest Tumblr YouTube