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

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,...

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Main Authors: Chung, I-Hsiao, Liu, Hsuan, Lin, Yang-Hsiang, Chi, Hsiang-Cheng, Huang, Ya-Hui, Yang, Chang-Ching, Yeh, Chau-Ting, Tan, Bertrand Chin-Ming, Lin, Kwang-Huei
Format: Online
Language:English
Published: Impact Journals LLC 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008372/
id pubmed-5008372
recordtype oai_dc
spelling pubmed-50083722016-09-12 ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance Chung, I-Hsiao Liu, Hsuan Lin, Yang-Hsiang Chi, Hsiang-Cheng Huang, Ya-Hui Yang, Chang-Ching Yeh, Chau-Ting Tan, Bertrand Chin-Ming Lin, Kwang-Huei Research Paper 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. Impact Journals LLC 2016-03-08 /pmc/articles/PMC5008372/ /pubmed/26968954 http://dx.doi.org/10.18632/oncotarget.7988 Text en Copyright: © 2016 Chung et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Chung, I-Hsiao
Liu, Hsuan
Lin, Yang-Hsiang
Chi, Hsiang-Cheng
Huang, Ya-Hui
Yang, Chang-Ching
Yeh, Chau-Ting
Tan, Bertrand Chin-Ming
Lin, Kwang-Huei
spellingShingle Chung, I-Hsiao
Liu, Hsuan
Lin, Yang-Hsiang
Chi, Hsiang-Cheng
Huang, Ya-Hui
Yang, Chang-Ching
Yeh, Chau-Ting
Tan, Bertrand Chin-Ming
Lin, Kwang-Huei
ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance
author_facet Chung, I-Hsiao
Liu, Hsuan
Lin, Yang-Hsiang
Chi, Hsiang-Cheng
Huang, Ya-Hui
Yang, Chang-Ching
Yeh, Chau-Ting
Tan, Bertrand Chin-Ming
Lin, Kwang-Huei
author_sort Chung, I-Hsiao
title ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance
title_short ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance
title_full ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance
title_fullStr ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance
title_full_unstemmed ChIP-on-chip analysis of thyroid hormone-regulated genes and their physiological significance
title_sort chip-on-chip analysis of thyroid hormone-regulated genes and their physiological significance
description 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.
publisher Impact Journals LLC
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008372/
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