Cadmium response of Csrp1 depends on MTF-1
Csrp1 was found in microarray analyses to be significantly downregulated in cadmium-treated Mtf1Mx-cre mice compared to Mtf1loxP mice (Table 1, c). CSRP1 is a member of the evolutionary conserved CRP family of proteins that have been implicated in myogenesis and cytoskeletal remodeling (41,42).
Semiquantitative RT–PCRs confirmed the microarray results, namely, that Csrp1 expression is elevated in Mtf1loxP livers upon cadmium exposure (Figure 4a). In contrast, no cadmium response was detectable in livers from Mtf1Mx-cre mice, suggesting that MTF-1 is required for cadmium induction of Csrp1.
Three MRE core consensus sequences were found upstream of the Csrp1 transcription start (MRE2 to MRE4, −56 to −366 bp), one was found immediately downstream (MRE1, +7 bp; Figure 4b). Specific binding of MTF-1 was observed with EMSA for MRE2 oligonucleotide and protein extract from an Mtf1loxP liver, but not an Mtf1Mx-cre liver extract lacking MTF-1, confirming the participation of MTF-1 in the complex (Figure 4c).