Differential transcriptional regulation by mouse single-minded 2s.
Single-minded 1 and 2 are unique members of the basic helix-loop-helix Per-Arnt-Sim family as they are transcriptional repressors. Here we report the identification and transcriptional characterization of mouse Sim2s, a splice variant of Sim2, which is missing the carboxyl Pro/Ala-rich repressive domain. Sim2s is expressed at high levels in kidney and skeletal muscle; however, the ratio of Sim2 to Sim2s mRNA differs between these tissues. Similar to full-length Sim2, Sim2s interacts with Arnt and to a lesser extent, Arnt2. The effects of Sim2s on transcriptional regulation through hypoxia, dioxin, and central midline response elements are different than that of full-length Sim2. Specifically, Sim2s exerts a less repressive effect on hypoxia-induced gene expression than full-length Sim2, but is just as effective as Sim2 at repressing TCDD-induced gene expression from a dioxin response element. Interestingly, Sim2s bind to and activates expression from a central midline response element-controlled reporter through an Arnt transactivation domain-dependent mechanism. The differences in expression pattern, protein interactions, and transcriptional activities between Sim2 and Sim2s may reflect differential roles each isoform plays during development or in tissue-specific effects on other protein-mediated pathways.
Department of Integrated Biosciences, College of Veterinary Medicine, Texas A&M University, College Station, Texas 77843-4458, USA.
Richard P
RP
Metz
Hyeong-Il
HI
Kwak
Tanya
T
Gustafson
Brian
B
Laffin
Weston W
WW
Porter
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004147:Dioxins / Q000737:chemistry; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D000860:Hypoxia; D047468:Immunoprecipitation; D007668:Kidney / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D020218:Response Elements; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D014018:Tissue Distribution; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D004147:Dioxins; D008156:Luciferases; D020033:Protein Isoforms; D012313:RNA; C486578:Sim2 protein, mouse