ZBP-89 represses vimentin gene transcription by interacting with the transcriptional activator, Sp1.
Vimentin, a member of the intermediate filament protein family, is regulated both developmentally and tissue specifically. It is also a marker of the metastatic potential of many tumor cells. Pre viously, the human vimentin promoter has been shown to contain multiple elements for the binding of both positive- and negative-acting regulatory factors. Transient transfection analysis of various vimentin 5'-end promoter sequences and mutants thereof fused to a reporter gene further defined two regulatory elements, a positive element that binds Sp1 and a negative element that binds the protein ZBP-89. ZBP-89 has been shown to be either a repressor or an activator of gene expression, depending on the promoter. Here, we show that for vimentin, both ZBP-89 and ZBP-99 repress reporter gene expression in Schneider (S2) cells. Deletion constructs confirm that the glutamine-rich region of Sp1 is required to enhance vimentin transcription, whereas the N-terminus of ZBP-89 is required to interact with Sp1 and repress gene expression. The overexpression of hTAF(II)130 can alleviate ZBP-89 repression in S2 cells, suggesting how ZBP-89 might serve to block gene expression.
Zhang
Xueping
X
Department of Biochemistry and the Massey Cancer Center, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, VA 23298-0614, USA.
Diab
Iman H
IH
Zehner
Zendra E
ZE
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020868:Gene Silencing; D005973:Glutamine / Q000032:analysis; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020218:Response Elements; D017384:Sequence Deletion; D016329:Sp1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051705:Sp3 Transcription Factor; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism; D015534:Trans-Activators; D035362:Transcription Factor TFIID / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation; D014746:Vimentin / Q000235:genetics*
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; C101882:TAF4 protein, human; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D014746:Vimentin; C110951:ZNF148 protein, human; C120370:ZNF281 protein, human; D005973:Glutamine; D051705:Sp3 Transcription Factor