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Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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Thyroid transcription factor FOXE1 interacts with ETS factor ELK1 to co-regulate TERT
Martyn Bullock1, Grace Lim1, Cheng Li1,2
1Cancer Genetics Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia.
Oncotarget
|November 17, 2016
Summary
FOXE1 transcription factor interacts with ELK1, regulating thyroid cancer genes TERT and TPO. This interaction reveals a new pathway for thyroid function and cancer risk associated with FOXE1 variants.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- FOXE1 is crucial for thyroid development and linked to thyroid cancer risk.
- Its role in adult thyroid cancer remains unclear.
- Identifying FOXE1 partners may uncover oncogenic regulatory pathways.
Purpose of the Study:
- To investigate FOXE1 interactions and their role in thyroid cancer.
- To identify key transcriptional partners of FOXE1.
- To elucidate regulatory pathways involved in FOXE1-mediated oncogenesis.
Main Methods:
- Transcription factor-binding array identified ELK1 binding to FOXE1.
- Immunoprecipitation (IP) and mammalian two-hybrid assays confirmed physical association.
- Chromatin IP (ChIP) and gene reporter assays analyzed interactions on target gene promoters (TERT, TPO).
Main Results:
- FOXE1 physically binds to ELK1 in thyroid cells and human tissue.
- Both factors bind to TERT and TPO gene promoters.
- FOXE1 positively regulates TERT expression via ELK1.
- MEK inhibitor U0126 disrupts FOXE1-ELK1 interaction and reduces TERT/TPO promoter activity.
Conclusions:
- FOXE1 interacts with ELK1 on thyroid gene promoters, defining a novel regulatory pathway.
- Co-regulation of TERT by FOXE1 and ELK1 provides a mechanism for thyroid cancer risk associated with FOXE1 variants.
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