title: ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance.
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.
authors.affiliation: Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: I-Hsiao
authors.initials: IH
authors.lastname: Chung
authors.affiliation: Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.|Colorectal Section, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Hsuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yang-Hsiang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chi
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.|Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chang-Ching
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.|Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Department of Neurosurgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Bertrand Chin-Ming
authors.initials: BC
authors.lastname: Tan
authors.affiliation: Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan.|Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Kwang-Huei
authors.initials: KH
authors.lastname: Lin
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D047369:Chromatin Immunoprecipitation / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D014284:Triiodothyronine; C101003:ELF2 protein, human
keywords: ChIP-on-chip; ELF2; cell growth; thyroid hormone receptor