Identification of the p53 family-responsive element in the promoter region of the tumor suppressor gene hypermethylated in cancer 1.
Details
Serval ID
serval:BIB_878703EFA5D2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of the p53 family-responsive element in the promoter region of the tumor suppressor gene hypermethylated in cancer 1.
Journal
Oncogene
ISSN
0950-9232 (Print)
ISSN-L
0950-9232
Publication state
Published
Issued date
30/03/2006
Peer-reviewed
Oui
Volume
25
Number
14
Pages
2030-2039
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
The tumor suppressor gene hypermethylated in cancer 1 (HIC1), located on human chromosome 17p13.3, is frequently silenced in cancer by epigenetic mechanisms. Hypermethylated in cancer 1 belongs to the bric à brac/poxviruses and zinc-finger family of transcription factors and acts by repressing target gene expression. It has been shown that enforced p53 expression leads to increased HIC1 mRNA, and recent data suggest that p53 and Hic1 cooperate in tumorigenesis. In order to elucidate the regulation of HIC1 expression, we have analysed the HIC1 promoter region for p53-dependent induction of gene expression. Using progressively truncated luciferase reporter gene constructs, we have identified a p53-responsive element (PRE) 500 bp upstream of the TATA-box containing promoter P0 of HIC1, which is sequence specifically bound by p53 in vitro as assessed by electrophoretic mobility shift assays. We demonstrate that this HIC1 p53-responsive element (HIC1.PRE) is necessary and sufficient to mediate induction of transcription by p53. This result is supported by the observation that abolishing endogenous wild-type p53 function prevents HIC1 mRNA induction in response to UV-induced DNA damage. Other members of the p53 family, notably TAp73beta and DeltaNp63alpha, can also act through this HIC1.PRE to induce transcription of HIC1, and finally, hypermethylation of the HIC1 promoter attenuates inducibility by p53.
Keywords
Amino Acid Sequence, Base Sequence, Cell Line, Tumor, DNA Methylation, DNA Primers, DNA-Binding Proteins/genetics, Electrophoretic Mobility Shift Assay, Genes, Reporter, Genes, p53, Humans, Kruppel-Like Transcription Factors, Molecular Sequence Data, Promoter Regions, Genetic, RNA, Messenger/genetics, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Nucleic Acid, Transcription Factors/genetics, Up-Regulation
Pubmed
Web of science
Publisher's website
Open Access
Yes
Create date
08/03/2021 16:32
Last modification date
13/03/2021 6:26