ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance
Metrics: PDF 2143 views | HTML 2214 views | ?
I-Hsiao Chung1*, Hsuan Liu1,2,6*, Yang-Hsiang Lin1, Hsiang-Cheng Chi1, Ya-Hui Huang3, Chang-Ching Yang2,4, Chau-Ting Yeh3, Bertrand Chin-Ming Tan2,4,5, Kwang-Huei Lin1,3
1Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan
2Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
3Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
4Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
5Department of Neurosurgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
6Colorectal Section, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
*These authors have contributed equally to this work
Bertrand Chin-Ming Tan, e-mail: [email protected]
Kwang-Huei Lin, e-mail: [email protected]
Keywords: thyroid hormone receptor, ChIP-on-chip, cell growth, ELF2
Received: October 30, 2015 Accepted: February 23, 2016 Published: March 8, 2016
Triiodothyronine (T3) and its receptor (TR) modulate several physiological processes, including cell development, proliferation, differentiation and metabolism. The regulatory mechanism of T3/TR involves binding to the thyroid hormone response element (TRE) within the target gene promoter. However, the number of target genes directly regulated by TRα1 and the specific pathways of TR-regulated target genes remain largely unknown. Here, we expressed TRα1 in a HepG2 cell line and used chromatin immunoprecipitation coupled with microarray to determine the genes that are directly regulated by TRα1 and also involved in cell metabolism and proliferation. Our analysis identified E74-like factor 2 (ELF2), a transcription factor associated with tumor growth, as a direct target downregulated by T3/TR. Overexpression of ELF2 enhanced tumor cell proliferation, and conversely, its knockdown suppressed tumor growth. Additionally, ELF2 restored the proliferative ability of hepatoma cells inhibited by T3/TR. Our findings collectively support a potential role of T3/TR in tumor growth inhibition through regulation of ELF2.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.