title: Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts.
abstract: 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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Donald W. Reynolds Department of Geriatrics, The University of Arkansas for Medical Sciences and Geriatric Research, Education, and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.forename: Gohar
authors.initials: G
authors.lastname: Azhar
authors.forename: Scott
authors.initials: S
authors.lastname: Helms
authors.forename: Brian
authors.initials: B
authors.lastname: Burton
authors.forename: Chris
authors.initials: C
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhong
authors.forename: Xuesong
authors.initials: X
authors.lastname: Gu
authors.forename: Hong
authors.initials: H
authors.lastname: Fang
authors.forename: Weida
authors.initials: W
authors.lastname: Tong
authors.forename: Jeanne Y
authors.initials: JY
authors.lastname: Wei