Schnurri transcription factors from Drosophila and vertebrates can mediate Bmp signaling through a phylogenetically conserved mechanism.
Bone Morphogenetic Proteins (Bmps) are secreted growth factors that play crucial roles in animal development across the phylogenetic spectrum. Bmp signaling results in the phosphorylation and nuclear translocation of Smads, downstream signal transducers that bind DNA. In Drosophila, the zinc finger protein Schnurri (Shn) plays a key role in signaling by the Bmp2/Bmp4 homolog Decapentaplegic (Dpp), by forming a Shn/Smad repression complex on defined promoter elements in the brinker (brk) gene. Brk is a transcriptional repressor that downregulates Dpp target genes. Thus, brk inhibition by Shn results in the upregulation of Dpp-responsive genes. We present evidence that vertebrate Shn homologs can also mediate Bmp responsiveness through a mechanism similar to Drosophila Shn. We find that a Bmp response element (BRE) from the Xenopus Vent2 promoter drives Dpp-dependent expression in Drosophila. However, in sharp contrast to its activating role in vertebrates, the frog BRE mediates repression in Drosophila. Remarkably, despite these opposite transcriptional polarities, sequence changes that abolish cis-element activity in Drosophila also affect BRE function in Xenopus. These similar cis requirements reflect conservation of trans-acting factors, as human Shn1 (hShn1; HIVEP1) can interact with Smad1/Smad4 and assemble an hShn1/Smad complex on the BRE. Furthermore, both Shn and hShn1 activate the BRE in Xenopus embryos, and both repress brk and rescue embryonic patterning defects in shn mutants. Our results suggest that vertebrate Shn proteins function in Bmp signal transduction, and that Shn proteins recruit coactivators and co-repressors in a context-dependent manner, rather than acting as dedicated activators or repressors.
Yao
Li-Chin
LC
Department of Developmental and Cell Biology, and the Developmental Biology Center, University of California Irvine, Irvine, CA 92697, USA.
Blitz
Ira L
IL
Peiffer
Daniel A
DA
Phin
Sopheap
S
Wang
Ying
Y
Ogata
Souichi
S
Cho
Ken W Y
KW
Arora
Kavita
K
Warrior
Rahul
R
D000818:Animals; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000145:classification* / Q000235:genetics* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010802:Phylogeny; D020218:Response Elements / Q000235:genetics*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism; D014981:Xenopus / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C063232:HIVEP1 protein, human; D018398:Homeodomain Proteins; D051785:Smad Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C064196:dpp protein, Drosophila; C094066:shn protein, Drosophila; C099992:ventx2.1 protein, Xenopus