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Histone deacetylase-1 represses transcription by interacting with zinc-fingers and interfering with the DNA binding activity of Sp1

Authors
 Kang J.-E.  ;  Kim M.-H.  ;  Lee J.-A.  ;  Park H.  ;  Min-Nyung L.  ;  Auh C.-K.  ;  Hur M.-W 
Citation
 CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, Vol.16(1~3) : 23-30, 2005 
Journal Title
 CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 
ISSN
 1015-8987 
Issue Date
2005
MeSH
Sp1 ; Histone deacetylase 1 ; GC-box ; Trichostatin A, TSA ; Transcription ; Repression
Keywords
Sp1 ; Histone deacetylase 1 ; GC-box ; Trichostatin A, TSA ; Transcription ; Repression
Abstract
Sp1 activates the transcription of many cellular and viral genes, and histone deacetylase 1 (HDAC1) removes the acetyl group of nucleosomal core histones. Treatment of cells with the histone deacetylase 1 inhibitor, TSA, robustly activates the transcription of the Sp1-dependent promoters, suggesting the inhibition of Sp1 activity which is critical in the activation of transcription, by HDAC1. We assessed the protein-protein interactions occurring between Sp1 and HDAC1, and the transcriptional regulatory mechanism controlled by this interaction. In vitro GST fusion pull down assays, co-immunoprecipitation, and mammalian two-hybrid assays revealed that the HDAC1 noncatalytic domain (a.a. 237-482) interacts directly with the zinc-finger DNA binding domain of Sp1. DNase I footprinting revealed that this interaction prevents the binding of Sp1 zinc-fingers to the target GC-box. Gal4-HDAC1 fusion, targeted proximally to the GC-boxes, potently repressed the transcription of pG5-5x(GC)-Luc, in which Sp1 potently activates transcription. This repression of transcription does not involve the deacetylase activity of HDAC1, and is accomplished by the direct protein-protein interactions which occur between the Sp1 zinc-finger DNA binding domain and HDAC1, which interferes with the promoter GC-box binding of Sp1.
Full Text
http://www.karger.com/Article/FullText/87728
DOI
10.1159/000087728
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myung Hwa(김명화)
Park, Hye Jin(박혜진)
Lee, J. A.(이정안)
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/150027
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