Journal article
Expression of AP-2α in SV40 immortalized human lung fibroblasts is associated with a distinct pattern of cytosine methylation in the AP-2α promoter
Biochimica et biophysica acta. Gene structure and expression, Vol.1519(1), pp.85-91
2001
DOI: 10.1016/S0167-4781(01)00227-5
PMID: 11406275
Abstract
Activator protein-2α (AP-2α) is a cell type-specific, developmentally regulated, transcription factor that has been implicated as a critical regulator of gene expression during vertebrate development and carcinogenesis. We found that AP-2α was differentially expressed in the normal human lung fibroblast cell strains WI38, MRC-5 and their respective SV40-transformed cell counterparts WI38-VA, MRC-5VA. Since CpG methylation within genetic regulatory regions has been implicated as a mechanism of gene regulation, we investigated the CpG methylation status of the AP-2α gene promoter in these cells. High resolution mapping of methylated cytosines revealed that differential expression of the AP-2α gene in normal human lung fibroblasts and their SV40-transformed counterparts was associated with distinct patterns of cytosine methylation in the AP-2α promoter just 5′ to the transcription initiation site. Site-specific methylation was positively correlated with increased AP-2α gene expression in both transformed cell lines investigated. Interestingly, one of the two major centers of hypermethylation in the transformed cells encompassed the
cis-element for the AP-2 repressing transcription factor AP-2rep (KLF12). Finally, a sequence variation in human lung fibroblasts relative to the published sequence revealed a previously unidentified AP-2 binding site at position −528 with respect to the transcription initiation site that overlapped the AP-2rep site. Our results suggest that transcriptional activation of AP-2α in the SV40-transformed cells is mediated, at least in part, by site-specific methylation of a negative regulatory
cis-element in the AP-2α promoter.
Details
- Title: Subtitle
- Expression of AP-2α in SV40 immortalized human lung fibroblasts is associated with a distinct pattern of cytosine methylation in the AP-2α promoter
- Creators
- Chun-Hong ZhuYuanhui HuangMichael T BromanFrederick E Domann
- Resource Type
- Journal article
- Publication Details
- Biochimica et biophysica acta. Gene structure and expression, Vol.1519(1), pp.85-91
- DOI
- 10.1016/S0167-4781(01)00227-5
- PMID
- 11406275
- NLM abbreviation
- Biochim Biophys Acta
- ISSN
- 0167-4781
- eISSN
- 1879-2634
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 2001
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047650802771
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