In vitro analysis of the tissue plasminogen activator promoter reveals a GC box-binding activity present in murine brain but undetectable in kidney and liver.
Tissue plasminogen activator (t-PA) mRNA levels are high in murine brain, lower in kidney, and undetectable in liver. Differences in t-PA mRNA levels are regulated in part at the transcriptional level. Brain, kidney, and liver nuclear extracts direct regulated transcription from the murine t-PA promoter in a manner that reflects the relative levels of t-PA gene expression in these tissues in vivo. Analysis of mutants has defined two GC box motifs as important elements for regulated transcription in vitro. Upon investigation of protein-DNA binding, we detected an activity in brain extracts which was not detected in kidney or liver extracts. An Sp1-like factor also binds to this region in all three tissue types. DNA interference experiments show that the brain-enriched binding activity and the Sp1-like factor contact the same GC-rich sequences. These studies provide additional evidence that brain-enriched DNA-binding activities can interact with sequences also recognized by ubiquitous transcription factors.
Pecorino
L T
LT
Program in Cellular and Developmental Biology, State University of New York, Stony Brook 11794-8651.
Darrow
A L
AL
Strickland
S
S
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D001921:Brain / Q000201:enzymology*; D002467:Cell Nucleus / Q000502:physiology; D004247:DNA / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009710:Nucleotide Mapping; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D010959:Tissue Plasminogen Activator / Q000235:genetics*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D012313:RNA; D004247:DNA; D010959:Tissue Plasminogen Activator