Supplementary Figure 7: Mouse-specific mutation in GATA-3 binding motif of Gpr15 enhancer region.

Mouse-specific mutation in GATA-3 binding motif of Gpr15 enhancer region. An ~3000 bp, evolutionarily conserved region downstream of the GPR15 gene contains a cluster of TFBSs that are capable of integrating known GPR15-inducing signals. The conserved sequence is embedded in a region that is transcriptionally active (positions indicated in the figure) in GPR15-expressing cells (GM12878) but not in non GPR15-expressing cells. Two MA0037.2 GATA-3 consensus sites (JASPAR transcription factor database) are conserved in primates but not rodents (see Figure 6; one of the two similar sites is shown). A destructive mouse-specific A-to-G mutation in a GATA-3 binding site (MA0037.1 motif) adjacent to the highly conserved STAT-6 binding site is highlighted in blue. GPR15 expression is also from the ENCODE consortium (NCBI GEO accession number GSE19090, Affymetrix exon expression array): GM12878 cells had a strong GPR15 signal (+++, raw expression value 2733.13 ± 232.82, n = 3), correlating with strong active promoter activity, whereas the other cells lines with repressive or only weak enhancer marks at the GPR15 enhancer locus lacked GPR15 expression (NS; expression value < 53 in each case).