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Identification of target genes of oncogenic transcription factors
1McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706, USA.
Abstract:
Disregulation of many transcription factors is associated with the development of human neoplasia. Transcription factors regulate cell growth, differentiation, and apoptosis by binding to specific DNA sequences within the promoter regions of growth-regulatory genes and modulating expression of these genes. This simple model is complicated by the fact that mammalian transcription factors are often members of large protein families that bind to similar DNA sequences. This raises the question as to whether members of a particular family regulate expression of overlapping or unique sets of genes. This review is focused on addressing this question using the Ets, Myc, and E2F transcription factor families as examples. Deregulated activity of some, but not all, members of these families is observed in cancer. Here, we summarize the data illustrating the concept that binding of individual members of these families of factors can result in promoter-specific responses and review the studies that have provided some insight into how target gene specificity is achieved. Since, for all of these oncogenic transcription factors, it remains unclear exactly which target genes are important in neoplasia, we have also reviewed the many approaches researchers are using to identify target genes of the various Ets, Myc, and E2F family members.
Insights
Transcription factors regulate genes, but families like Ets, Myc, and E2F show varied roles in cancer. Understanding their specific gene targets is key to cancer research.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Transcription factors (TFs) are crucial for regulating cell processes like growth and apoptosis.
- Disregulation of TFs is linked to human neoplasia (cancer).
- Mammalian TFs often belong to large families with overlapping DNA-binding specificities, raising questions about gene regulation.
Purpose of the Study:
- To investigate whether members of TF families regulate overlapping or unique sets of genes.
- To use the Ets, Myc, and E2F transcription factor families as models to explore TF specificity.
- To review how target gene specificity is achieved by individual TF family members.
Main Methods:
- Review of existing literature on Ets, Myc, and E2F transcription factor families.
- Analysis of studies demonstrating promoter-specific responses to individual TF family members.
- Examination of research approaches for identifying TF target genes in neoplasia.
Main Results:
- Deregulated activity of specific members within the Ets, Myc, and E2F families is observed in cancer.
- Evidence suggests that individual TF family members can elicit promoter-specific gene expression responses.
- The precise target genes critical for neoplasia remain largely undefined for these oncogenic TFs.
Conclusions:
- TF family members exhibit distinct roles in gene regulation and cancer development.
- Understanding TF target gene specificity is essential for deciphering their roles in neoplasia.
- Identifying the specific target genes of Ets, Myc, and E2F is an active area of cancer research.