Selective modulation of the SM22alpha promoter by the binding of BTEB3 (basal transcription element-binding protein 3) to TGGG repeats.
We have previously identified a C2H2 zinc-finger transcription factor [BTEB3 (basal transcription element-binding protein 3)/KLF13 (Krüppel-like factor 13)] that activates the minimal promoter for the smooth muscle-specific SM22alpha gene in other types of cell. We show that recombinant BTEB3 binds to three TGGG motifs in the minimal SM22alpha promoter. By mutation analysis, only one of these boxes is required for BTEB3-dependent promoter activation in P19 cells and BTEB3 activates or inhibits reporter gene expression depending on the TGGG box to which it binds. Transient transfection experiments show that BTEB3 also activates reporter gene expression from the SM22alpha promoter in VSMCs (vascular smooth muscle cells). Similar studies showed that BTEB3 did not activate expression from the promoter regions of the smooth muscle myosin heavy chain or smooth muscle alpha-actin promoters, which contain similar sequences, implying that promoter activation by BTEB3 is selective. The expression of BTEB3 is readily detectable in VSMCs in vitro and is modulated in response to injury in vivo.
Martin
Karen M
KM
Section of Cardiovascular Biology, Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, U.K.
Ellis
Peter D
PD
Metcalfe
James C
JC
Kemp
Paul R
PR
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D020212:Carotid Artery Injuries / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D008840:Microfilament Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D009124:Muscle Proteins / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D008840:Microfilament Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C058992:Tagln protein, mouse; D015534:Trans-Activators; C051615:transgelin; D004247:DNA