fig1

Figure 1. Serum response factor (SRF) association with fundamental cofactors. (A) Schematic diagram of the SRF regulatory domains including a highly conserved DNA-binding/dimerization domain of 90 amino acids termed the MADS box^[4] and its transcriptional activation domain (TAD). (B) MADS box DNA contact sites and biophysical structures defined by X-ray crystal analysis^[7] revealed the N-terminal extension (132-152 aa) that contacts the minor groove of the CArG box half site. Next, alpha I helices (153-179 aa) lie parallel and on top of a narrow DNA major groove and are followed by two beta-sheets separated by the beta-loop (190-199 aa), thus allowing for dimerization of the monomers. A second alpha II helix (204-224 aa) in the C-terminal portion of the MADS box completes the structure. (C) The STRING program (https://string-db.org/network/10090.ENSMUSP00000015749) identified the top 10 factors that have the strongest association with SRF to generate the network images for predicted associations with SRF (a node) and for cofactor proteins (second nodes). An edge may be drawn with up to seven differently colored lines which represent the existence of types of evidence used in predicting the associations: blue line (co-occurrence), purple line (experiments), yellow line (text mining), light blue line (database), and black line (co-expression). (D) The highest confidence scores are mostly above 0.9. These are the strongest enrichment scores supporting the importance of these proteins’ biological functional activity connected to SRF. (E) The schematic diagram of the SRF regulatory domains including the MADS box shows that the cofactors NKX2-5, GATA4/6, and CRP2 and inhibitor HOP1 bind to the N-terminal extension. ETS factors ELK1 and SAP1 bind to the beta loop and compete with MRTF-A. TEAD factors bind to the second alpha helix. YAP may indirectly bind to SRF through MRTF-A and TEAD interaction sites.