Expression and comparative genomics of two serum response factor genes in zebrafish

Abstract

Serum response factor (SRF) is a single copy, highly conserved transcription factor that governs the expression of hundreds of genes involved with actin cytoskeletal organization, cellular growth and signaling, neuronal circuitry and muscle differentiation. Zebrafish have emerged as a facile and inexpensive vertebrate model to delineate gene expression, regulation, and function, and yet the study of SRF in this animal has been virtually unexplored. Here, we report the existence of two srf genes in zebrafish, with partially overlapping patterns of expression in 3 and 7 day old developing animals. The mammalian ortholog (srf1) encodes for a 520 amino acid protein expressed in adult vascular and visceral smooth muscle cells, cardiac and skeletal muscle, as well as neuronal cells. The second zebrafish srf gene (srf2), encoding for a presumptive protein of only 314 amino acids, is transcribed at lower levels and appears to be less widely expressed across adult tissues. Both srf genes are induced by the SRF coactivator myocardin and attenuated with a short hairpin RNA to mammalian SRF. Promoter studies with srf1 reveal conserved CArG boxes that are the targets of SRF-myocardin in embryonic zebrafish cells. These results reveal that SRF was duplicated in the zebrafish genome and that its protein expression in all three muscle cell types is highly conserved across vertebrate animals suggesting an ancient code for transcriptional regulation of genes unique to muscle cell lineages.

Redox Modification of Nuclear Actin by MICAL-2 Regulates SRF Signaling

“…We found that many cardiac muscle-specific SRF/MRTF-A target genes, such as cardiac alpha actin , smooth muscle alpha actin , cardiac actin smooth muscle , skeletal alpha actin , smooth muscle 22a , srf , and calponin (Chong et al, 2012; Davis et al, 2008; Descot et al, 2009) were markedly reduced in mical2b knockdown animals (Figure 5H). The control genes vascular endothelial growth factor ( vegf ), fibroblast growth factor 4 ( fgf4 ), and ETS translocation variant 4 ( pea3) which regulate MRTF-A-independent cardiac development in zebrafish, were not affected by mical2b knockdown (Figure 5H) (Liang et al, 2001; Znosko et al, 2010).…”

Characterization of vascular mural cells during zebrafish development

“…These markers include mainly contractile, cytoskeletal and cytoskeleton-associated proteins such as smooth muscle alpha-actin, Sm22alpha, smooth muscle myosin heavy chain, and Smoothelin. Similarly, in zebrafish, the heterogeneity of MCs precludes their identification by single markers (Georgijevic et al, 2007; Davis et al, 2008). Therefore, we identified and cloned a panel of zebrafish MC markers including the genes encoding Transgelin (Sm22alpha-b), Transgelin2 (Sm22alpha-a), Acta2, Myh11, Smoothelin, Calponin, and Desmin.…”

Serum Response Factor in muscle tissues: from development to ageing

“…S RF, a conserved transcription factor during evolution and encoded by a single gene with the exception of zebrafish, 1 is at the confluence of multiple signalling pathways controlling the transcription of immediate-early response genes and muscle-specific genes. 2 It is a member of the MADS box family of transcription factors, and binds the core sequence of CArG boxes [CC (A/T) 6 GG] as a homodimer 2 .…”