Abstract
Human Kruppel-like factor 5 (hKLF5) is a transcription factor with a potential tumor suppressor function in prostate and breast cancers. In the majority of cancer samples examined, a significant loss of expression for KLF5 has been detected. Whereas hemizygous deletion appears to be responsible for KLF5's reduced expression in about half of the cases, the mechanism for reduction is unknown in the remaining half; gene promoter methylation does not appear to be involved. In this report, we studied the regulation of KLF5 and cloned and functionally characterized a 1944-bp fragment of the 5′-flanking region of the hKLF5 gene. Several mitogens as well as global demethylation induced the expression of KLF5, implicating multiple factors in the regulation of KLF5. KLF5's promoter lacks a TATA box and has a GC-rich region. Deletion mapping in combination with promoter activity assay showed that multiple cis-elements are involved in the transcriptional regulation of KLF5, some of which may play a repressor role whereas some others play an enhancer role. The Sp1 site between position -239 and -219 is essential for a basal promoter activity. Deletion or mutations of this Sp1 site significantly reduced promoter activity in several epithelial cell lines. Electrophoretic mobility shift assays (EMSAs) revealed that the Sp1 site binds Sp1 protein in nucleic extracts of different cell lines. In addition, overexpression of Sp1 protein transactivates KLF5 promoter activity. These findings suggest that Sp1 is a key transcription factor in KLF5's dynamic transcriptional regulation.
| Original language | English |
|---|---|
| Pages (from-to) | 133-142 |
| Number of pages | 10 |
| Journal | Gene |
| Volume | 330 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - 14 Apr 2004 |
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Keywords
- BFGF
- Basic fibroblast growth factor
- Cancer cell line
- Gene expression
- HKLF5
- KLF4
- KLF5
- Kruppel-like factor 4
- Kruppel-like factor 5
- PDGFa
- Platelet-derived growth factor a
- Promoter
- SMC
- T cell receptor
- TCR
- TGF-b
- Transforming growth factor b
Cite this
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Regulation of KLF5 involves the Sp1 transcription factor in human epithelial cells. / Chen, Ceshi; Zhou, Yingfa; Zhou, Zhongmei; Sun, Xiaodong; Otto, Kristen B.; Uht, Rosalie Maire; Dong, Jin Tang.
In: Gene, Vol. 330, No. 1-2, 14.04.2004, p. 133-142.Research output: Contribution to journal › Article
TY - JOUR
T1 - Regulation of KLF5 involves the Sp1 transcription factor in human epithelial cells
AU - Chen, Ceshi
AU - Zhou, Yingfa
AU - Zhou, Zhongmei
AU - Sun, Xiaodong
AU - Otto, Kristen B.
AU - Uht, Rosalie Maire
AU - Dong, Jin Tang
PY - 2004/4/14
Y1 - 2004/4/14
N2 - Human Kruppel-like factor 5 (hKLF5) is a transcription factor with a potential tumor suppressor function in prostate and breast cancers. In the majority of cancer samples examined, a significant loss of expression for KLF5 has been detected. Whereas hemizygous deletion appears to be responsible for KLF5's reduced expression in about half of the cases, the mechanism for reduction is unknown in the remaining half; gene promoter methylation does not appear to be involved. In this report, we studied the regulation of KLF5 and cloned and functionally characterized a 1944-bp fragment of the 5′-flanking region of the hKLF5 gene. Several mitogens as well as global demethylation induced the expression of KLF5, implicating multiple factors in the regulation of KLF5. KLF5's promoter lacks a TATA box and has a GC-rich region. Deletion mapping in combination with promoter activity assay showed that multiple cis-elements are involved in the transcriptional regulation of KLF5, some of which may play a repressor role whereas some others play an enhancer role. The Sp1 site between position -239 and -219 is essential for a basal promoter activity. Deletion or mutations of this Sp1 site significantly reduced promoter activity in several epithelial cell lines. Electrophoretic mobility shift assays (EMSAs) revealed that the Sp1 site binds Sp1 protein in nucleic extracts of different cell lines. In addition, overexpression of Sp1 protein transactivates KLF5 promoter activity. These findings suggest that Sp1 is a key transcription factor in KLF5's dynamic transcriptional regulation.
AB - Human Kruppel-like factor 5 (hKLF5) is a transcription factor with a potential tumor suppressor function in prostate and breast cancers. In the majority of cancer samples examined, a significant loss of expression for KLF5 has been detected. Whereas hemizygous deletion appears to be responsible for KLF5's reduced expression in about half of the cases, the mechanism for reduction is unknown in the remaining half; gene promoter methylation does not appear to be involved. In this report, we studied the regulation of KLF5 and cloned and functionally characterized a 1944-bp fragment of the 5′-flanking region of the hKLF5 gene. Several mitogens as well as global demethylation induced the expression of KLF5, implicating multiple factors in the regulation of KLF5. KLF5's promoter lacks a TATA box and has a GC-rich region. Deletion mapping in combination with promoter activity assay showed that multiple cis-elements are involved in the transcriptional regulation of KLF5, some of which may play a repressor role whereas some others play an enhancer role. The Sp1 site between position -239 and -219 is essential for a basal promoter activity. Deletion or mutations of this Sp1 site significantly reduced promoter activity in several epithelial cell lines. Electrophoretic mobility shift assays (EMSAs) revealed that the Sp1 site binds Sp1 protein in nucleic extracts of different cell lines. In addition, overexpression of Sp1 protein transactivates KLF5 promoter activity. These findings suggest that Sp1 is a key transcription factor in KLF5's dynamic transcriptional regulation.
KW - BFGF
KW - Basic fibroblast growth factor
KW - Cancer cell line
KW - Gene expression
KW - HKLF5
KW - KLF4
KW - KLF5
KW - Kruppel-like factor 4
KW - Kruppel-like factor 5
KW - PDGFa
KW - Platelet-derived growth factor a
KW - Promoter
KW - SMC
KW - T cell receptor
KW - TCR
KW - TGF-b
KW - Transforming growth factor b
UR - http://www.scopus.com/inward/record.url?scp=1842839974&partnerID=8YFLogxK
U2 - 10.1016/j.gene.2004.01.014
DO - 10.1016/j.gene.2004.01.014
M3 - Article
C2 - 15087132
AN - SCOPUS:1842839974
VL - 330
SP - 133
EP - 142
JO - Gene
JF - Gene
SN - 0378-1119
IS - 1-2
ER -