Transcriptional regulation of BMP4 synexpression in transgenic Xenopus

Abstract

Synexpression groups are genetic modules composed of genes that share both a complex expression pattern and the biological process in which they function. Here we investigate the regulation of BMP4 synexpression by studying the enhancers of bambi, smad7 and vent2 in Xenopus. We find that a BMP4 synexpression promoter module is compact and (i) requires direct BMP responsiveness through Smad and Smad-cofactor binding motifs, (ii) may contain an evolutionary conserved BMP-responsive element, bre7 (TGGCGCC), that is crucial for expression of bambi and smad7 and is highly prognostic for novel BMP-responsive enhancers (BREs); and (iii) requires a narrow window of BMP inducibility, because minor enhancement or reduction of BMP responsiveness abolishes synexpression. Furthermore, we used a bioinformatic model to predict in silico 13 novel BREs, and tested five of them that were found in the id1-4 genes. The results highlight that in vivo analysis is required to reveal the physiological, spatio-temporal regulation of BMP-responsive genes.

Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma

“…These were (1) co-expressed genes are likely to be coregulated (Niehrs and Pollet, 1999;Karaulanov et al, 2004) and (2) noncoding regulatory sequences tend to be evolutionarily conserved (Hardison et al, 1997;Wasserman et al, 2000). The assumption that overexpression of SOX4 modulates the transcrip- tional activity of member genes within its synexpression group was approached using both a bioinformatics and a biochemical strategy.…”

Finding partners: How BMPs select their targets

“…This may explain why relatively long concatemers of Smadbinding sites are often needed to obtain transcriptional activation in cell culture (Jonk et al, 1998;. The promoters of some BMP inducible genes (e.g., bambi, and the id and vent family genes) have numerous Smad-binding sites (López-Rovira et al, 2002;Korchynskyi and ten Dijke, 2002;Karaulanov et al, 2004), presumably to more efficiently recruit the Smads to enhance transcriptional regulation. While isolated MH1 domains of Smad3 do not show cooperative binding to palindromic SBEs (Shi et al, 1998), it is reasonable to believe that full-length Smads would behave differently.…”

“…Another link between vertebrate Schnurris and BMP signaling comes from examination of the cross-species behavior of a BRE from the Xenopus vent2 gene (Candia et al, 1997;Rastegar et al, 1999;Hata et al, 2000;Karaulanov et al, 2004;von Bubnoff et al, 2005). The BRE mediates BMP induction during frog gastrulation and is also found in the promoters of two other BMP target genes, id3 and bambi (Karaulanov et al, 2004;von Bubnoff et al, 2005).…”

“…The BRE mediates BMP induction during frog gastrulation and is also found in the promoters of two other BMP target genes, id3 and bambi (Karaulanov et al, 2004;von Bubnoff et al, 2005). Transgenic Drosophila lines bearing a vertebrate BRE-driven lacZ reporter gene have provided insight into how vertebrate target gene expression is regulated by BMPs.…”

Molecular genetic insights into deuterostome evolution from the direct-developing hemichordateSaccoglossus kowalevskii

“…The most striking feature of Bmp and chordin between vertebrates and arthropods is that their relative expression is inverted dorsoventrally with respect to each other (Arendt & Nü bler-Jung 1994, 1996De Robertis & Sasai 1996). In hemichordates, bmp2/4 is expressed along the dorsal midline throughout all stages of development, along with all the members of the Bmp synexpression group (Niehrs & Pollet 1999;Karaulanov et al 2004). At early developmental stages, chordin is expressed ventrally and very broadly, on the opposite side to bmp2/4, almost up to the dorsal midline, but is increasingly restricted to the ventral side as developmental progresses.…”