ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance

I-Hsiao Chung; Hsuan Liu; Yang-Hsiang Lin; Hsiang-Cheng Chi; Ya-Hui Huang; Chang-Ching Yang; Chau-Ting Yeh; Bertrand Chin-Ming Tan; Kwang-Huei Lin

doi:10.18632/oncotarget.7988

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Research Papers:

ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance

I-Hsiao Chung _, Hsuan Liu, Yang-Hsiang Lin, Hsiang-Cheng Chi, Ya-Hui Huang, Chang-Ching Yang, Chau-Ting Yeh, Bertrand Chin-Ming Tan and Kwang-Huei Lin

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Oncotarget. 2016; 7:22448-22459. https://doi.org/10.18632/oncotarget.7988

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Abstract

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

Correspondence to:

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

ABSTRACT

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.

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Research Papers:

ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance

Abstract