The zinc finger repressor, ZBP-89, recruits histone deacetylase 1 to repress vimentin gene expression.
Vimentin, a member of the intermediate filament (IF) protein family, exhibits a complex pattern of tissue- and developmental-specific expression. Although vimentin is widely expressed in the embryo, its expression becomes restricted during terminal differentiation. Moreover, it is often expressed in tissue culture cells despite their embryological origin and is a marker for the metastatic tumor cell. Previously, the vimentin promoter has been shown to contain several positive- and negative-acting cis-elements. The negative elements bind the transcription factor ZBP-89. Interestingly, ZBP-89 can be either an activator or a repressor of gene expression. For instance, ZBP-89 has been shown to activate p21(waf1/cip1) expression by recruiting p300 to the p21 promoter. Here, we have investigated the mechanism of ZBP-89 repression. The histone deacetylase (HDAC) inhibitor TSA enhances vimentin gene expression requiring the proximal promoter region including GC-box 1, a known Sp1/Sp3 binding site. Chromatin immunoprecipitation (ChIP) assays document an increase in the acetylation status of histone H3 on the endogenous vimentin gene concomitant with TSA treatment. However, EMSAs, DNA precipitation, co-immunoprecipitation and ChIP data show that it is not Sp1, but rather ZBP-89, which recruits HDAC1. From these studies we conclude that ZBP-89 functions as a repressor by recruiting HDAC1 to the vimentin promoter.
The Department of Biochemistry and the Massey Cancer Center, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, VA 23298-0614, USA.
Yongzhong
Y
Wu
Xueping
X
Zhang
Morgan
M
Salmon
Zendra E
ZE
Zehner
D000107:Acetylation / Q000187:drug effects; D001483:Base Sequence; D001665:Binding Sites; D002457:Cell Extracts; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D051705:Sp3 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014746:Vimentin / Q000235:genetics*; D016335:Zinc Fingers
D002457:Cell Extracts; D004268:DNA-Binding Proteins; D006657:Histones; D006877:Hydroxamic Acids; D046912:Multiprotein Complexes; D012333:RNA, Messenger; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D014746:Vimentin; C110951:ZNF148 protein, human; D051705:Sp3 Transcription Factor; C012589:trichostatin A; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases