Differential regulation of the insulin-like growth factor II mRNA-binding protein genes by architectural transcription factor HMGA2.
The developmentally regulated architectural transcription factor, high mobility group A2 (HMGA2), is involved in growth regulation and plays an important role in embryogenesis and tumorigenesis. Little is known, however, about its downstream targets. We performed a search for genes of which expression is strongly altered during embryonic development in two HMGA2-deficient mouse strains, which display a pygmy-phenotype, as compared to wild-type mice. We found that the insulin-like growth factor II mRNA-binding protein 2 gene (IMP2), but not its family members IMP1 and IMP3, was robustly downregulated in mutant E12.5 embryos. Furthermore, we show that wild-type HMGA2 and its tumor-specific truncated form have opposite effects on IMP2 expression. Our results clearly indicate that HMGA2 differentially regulates expression of IMP family members during embryogenesis.
Brants
Jan R
JR
Laboratory for Molecular Oncology, Department of Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology (VIB), Herestraat 49, B-3000 Leuven, Belgium.
Ayoubi
Torik A Y
TA
Chada
Kiran
K
Marchal
Kathleen
K
Van de Ven
Wim J M
WJ
Petit
Marleen M R
MM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D017931:DNA Primers; D005314:Embryonic and Fetal Development; D005786:Gene Expression Regulation / Q000235:genetics*; D025743:HMGA2 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
D017931:DNA Primers; D025743:HMGA2 Protein; C498779:IGF2BP2 protein, human; C498780:IGF2BP3 protein, human; C498777:Igf2bp3 protein, mouse; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D007335:Insulin-Like Growth Factor II