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Transcriptional profiling of Krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial
Xinming Chen1, Erika M Whitney, Shu Y Gao
1Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, 2101 Whitehead Research Building, Atlanta, GA 30322, USA.
Abstract:
Krüppel-like factor 4 (KLF4) is an epithelially enriched, zinc finger-containing transcription factor, the expression of which is associated with growth arrest. Constitutive expression of KLF4 inhibits G1/S transition of the cell cycle but the manner by which it accomplishes this effect is unclear. To better understand the biochemical function of KLF4, we identified its target genes using cDNA microarray analysis in an established human cell line containing inducible KLF4. RNA extracted from induced and control cells were hybridized differentially to microarray chips containing 9600 human cDNAs. In all, 84 genes with significantly increased expression and 107 genes with significantly reduced expression due to KLF4 induction were identified. The affected genes are sorted to several clusters on the basis of functional relatedness. A major cluster belongs to genes involved in cell-cycle control. Within this cluster, many up-regulated genes are inhibitors of the cell cycle and down-regulated genes are promoters of the cell cycle. Another up-regulated gene cluster includes nine keratin genes, of which seven are located in a specific region on chromosome 12. The results indicate that KLF4 is involved in the control of cell proliferation and does so by eliciting changes in expression of numerous cell-cycle regulatory genes in a concerted manner. Furthermore, KLF4 regulates expression of a group of epithelial-specific keratin genes in a manner consistent with a potential locus control region function.
Insights
Krüppel-like factor 4 (KLF4) controls cell growth by altering cell cycle gene expression. KLF4 also regulates epithelial keratin genes, suggesting a role in cell differentiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Krüppel-like factor 4 (KLF4) is a transcription factor found in epithelial cells.
- KLF4 expression is linked to growth arrest and inhibition of cell cycle progression.
- The precise mechanisms by which KLF4 affects the cell cycle are not fully understood.
Purpose of the Study:
- To elucidate the biochemical function of KLF4.
- To identify KLF4 target genes and understand their role in cell cycle regulation.
- To investigate KLF4's influence on epithelial-specific gene expression.
Main Methods:
- Utilized cDNA microarray analysis in a human cell line with inducible KLF4 expression.
- Compared gene expression profiles between KLF4-induced and control cells.
- Analyzed 9600 human cDNAs to identify differentially expressed genes.
Main Results:
- Identified 84 up-regulated and 107 down-regulated genes upon KLF4 induction.
- KLF4 significantly impacts genes involved in cell-cycle control, including up-regulation of inhibitors and down-regulation of promoters.
- Observed KLF4-mediated up-regulation of nine keratin genes, seven of which are clustered on chromosome 12.
Conclusions:
- KLF4 plays a crucial role in controlling cell proliferation by modulating numerous cell-cycle regulatory genes.
- KLF4 influences epithelial-specific keratin gene expression, potentially indicating a locus control region function.
- KLF4's coordinated regulation of target genes highlights its importance in cellular processes.