Regulation of KLF5 involves the Sp1 transcription factor in human epithelial cells

Ceshi Chen, Yingfa Zhou, Zhongmei Zhou, Xiaodong Sun, Kristen B. Otto, Rosalie Maire Uht, Jin Tang Dong

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 languageEnglish
Pages (from-to)133-142
Number of pages10
JournalGene
Volume330
Issue number1-2
DOIs
StatePublished - 14 Apr 2004

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Kruppel-Like Transcription Factors
Transcription Factors
Epithelial Cells
GC Rich Sequence
Cell Line
TATA Box
Sequence Deletion
5' Flanking Region
Electrophoretic Mobility Shift Assay
Mitogens
Methylation
Genes
Neoplasms
Prostatic Neoplasms
Proteins
Breast Neoplasms
Human Sp1 protein

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

Chen, C., Zhou, Y., Zhou, Z., Sun, X., Otto, K. B., Uht, R. M., & Dong, J. T. (2004). Regulation of KLF5 involves the Sp1 transcription factor in human epithelial cells. Gene, 330(1-2), 133-142. https://doi.org/10.1016/j.gene.2004.01.014
Chen, Ceshi ; Zhou, Yingfa ; Zhou, Zhongmei ; Sun, Xiaodong ; Otto, Kristen B. ; Uht, Rosalie Maire ; Dong, Jin Tang. / Regulation of KLF5 involves the Sp1 transcription factor in human epithelial cells. In: Gene. 2004 ; Vol. 330, No. 1-2. pp. 133-142.
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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.",
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Chen, C, Zhou, Y, Zhou, Z, Sun, X, Otto, KB, Uht, RM & Dong, JT 2004, 'Regulation of KLF5 involves the Sp1 transcription factor in human epithelial cells', Gene, vol. 330, no. 1-2, pp. 133-142. https://doi.org/10.1016/j.gene.2004.01.014

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 journalArticle

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

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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 -