To identify in vivo new cardiac SRF target genes and to study the response of these novel genes to SRF overexpression, we employed a cardiac-specific, transgenic mouse model that has a phenotype in young adulthood which resembles that of the typically aged heart. Using this “cardiac aging” model, we identified 207 genes that are important to cardiac function that were differentially expressed in vivo. Among them, 192 genes had SRF binding motifs (56 with CArG and 136 with CArG-like elements) in their promoter region. Fifty-one of 56 genes with classic CArG elements were not previously reported. These SRF target 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 were significantly increased. Using public databases of mouse models of stress, we also found that altered expression of the SRF target genes occurred in these hearts as well. Thus, SRF target genes are actively regulated under various physiological and pathological conditions, including hemodynamic stress. The mild elevation of SRF protein in the rodent heart that is observed during typical adult aging may have a major impact on many SRF target genes, thereby affecting cardiac structure and performance. In addition, these results could help to enhance our understanding of SRF regulation of cellular processes, including metabolic and cytoskeletal function. The generation and characterization of transgenic mice with mild cardiac-specific overexpression of SRF was previously reported (Zhang et al., 2003). At 6 months of age, the transgenic mice manifested cardiac changes suggestive of an “aged heart” (Zhang et al., 2003). Therefore, 6-month-old transgenic and non-transgenic mice were used in this study.
Overall design
Cardiac gene expression in SRF Tg heart was compared to that of wild-type mice.
A list of differentially expressed genes (DEGs) were identified using a t-test with a combination of cut off p-value (p<0.05) and fold change (FC>2) header descriptions
Symbol
Description
Fold-change
RefSeq
Data table
Symbol
Description
Fold-change
RefSeq
B4galnt1
beta-1,4-n-acetyl-galactosaminyl transferase 1
6.9733
NM_008080
Apod
Apolipoprotein d
3.6633
NM_007470
Pfkp
Phosphofructokinase, Platelet
2.0999
NM_019703
Acot9
Acyl-CoA Thioesterase 9
2.0078
NM_019736
Slc27a1
Solute Carrier Family 27 (fatty acid transporter), Member 1
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