Modulation of thyroid hormone-dependent gene expression in Xenopus laevis by INhibitor of Growth (ING) proteins.

INhibitor of Growth (ING) proteins belong to a large family of plant homeodomain finger-containing proteins important in epigenetic regulation and carcinogenesis. We have previously shown that ING1 and ING2 expression is regulated by thyroid hormone (TH) during metamorphosis of the Xenopus laevis ta...

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Main Authors: Caren C Helbing, Mary J Wagner, Katherine Pettem, Jill Johnston, Rachel A Heimeier, Nik Veldhoen, Frank R Jirik, Yun-Bo Shi, Leon W Browder
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3230625?pdf=render
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author Caren C Helbing
Mary J Wagner
Katherine Pettem
Jill Johnston
Rachel A Heimeier
Nik Veldhoen
Frank R Jirik
Yun-Bo Shi
Leon W Browder
author_facet Caren C Helbing
Mary J Wagner
Katherine Pettem
Jill Johnston
Rachel A Heimeier
Nik Veldhoen
Frank R Jirik
Yun-Bo Shi
Leon W Browder
author_sort Caren C Helbing
collection DOAJ
description INhibitor of Growth (ING) proteins belong to a large family of plant homeodomain finger-containing proteins important in epigenetic regulation and carcinogenesis. We have previously shown that ING1 and ING2 expression is regulated by thyroid hormone (TH) during metamorphosis of the Xenopus laevis tadpole. The present study investigates the possibility that ING proteins modulate TH action.Tadpoles expressing a Xenopus ING2 transgene (Trans(ING2)) were significantly smaller than tadpoles not expressing the transgene (Trans(GFP)). When exposed to 10 nM 3,5,3'-triiodothyronine (T(3)), premetamorphic Trans(ING2) tadpoles exhibited a greater reduction in tail, head, and brain areas, and a protrusion of the lower jaw than T(3)-treated Trans(GFP) tadpoles. Quantitative real time polymerase chain reaction (QPCR) demonstrated elevated TH receptor β (TRβ) and TH/bZIP transcript levels in Trans(ING2) tadpole tails compared to Trans(GFP) tadpoles while TRα mRNAs were unaffected. In contrast, no difference in TRα, TRβ or insulin-like growth factor (IGF2) mRNA abundance was observed in the brain between Trans(ING2) and Trans(GFP) tadpoles. All of these transcripts, except for TRα mRNA in the brain, were inducible by the hormone in both tissues. Oocyte transcription assays indicated that ING proteins enhanced TR-dependent, T(3)-induced TRβ gene promoter activity. Examination of endogenous T(3)-responsive promoters (TRβ and TH/bZIP) in the tail by chromatin immunoprecipitation assays showed that ING proteins were recruited to TRE-containing regions in T(3)-dependent and independent ways, respectively. Moreover, ING and TR proteins coimmunoprecipitated from tail protein homogenates derived from metamorphic climax animals.We show for the first time that ING proteins modulate TH-dependent responses, thus revealing a novel role for ING proteins in hormone signaling. This has important implications for understanding hormone influenced disease states and suggests that the induction of ING proteins may facilitate TR function during metamorphosis in a tissue-specific manner.
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spelling doaj.art-9deaa40913544dfb9e2c0c87f4c3755d2022-12-22T03:11:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01612e2865810.1371/journal.pone.0028658Modulation of thyroid hormone-dependent gene expression in Xenopus laevis by INhibitor of Growth (ING) proteins.Caren C HelbingMary J WagnerKatherine PettemJill JohnstonRachel A HeimeierNik VeldhoenFrank R JirikYun-Bo ShiLeon W BrowderINhibitor of Growth (ING) proteins belong to a large family of plant homeodomain finger-containing proteins important in epigenetic regulation and carcinogenesis. We have previously shown that ING1 and ING2 expression is regulated by thyroid hormone (TH) during metamorphosis of the Xenopus laevis tadpole. The present study investigates the possibility that ING proteins modulate TH action.Tadpoles expressing a Xenopus ING2 transgene (Trans(ING2)) were significantly smaller than tadpoles not expressing the transgene (Trans(GFP)). When exposed to 10 nM 3,5,3'-triiodothyronine (T(3)), premetamorphic Trans(ING2) tadpoles exhibited a greater reduction in tail, head, and brain areas, and a protrusion of the lower jaw than T(3)-treated Trans(GFP) tadpoles. Quantitative real time polymerase chain reaction (QPCR) demonstrated elevated TH receptor β (TRβ) and TH/bZIP transcript levels in Trans(ING2) tadpole tails compared to Trans(GFP) tadpoles while TRα mRNAs were unaffected. In contrast, no difference in TRα, TRβ or insulin-like growth factor (IGF2) mRNA abundance was observed in the brain between Trans(ING2) and Trans(GFP) tadpoles. All of these transcripts, except for TRα mRNA in the brain, were inducible by the hormone in both tissues. Oocyte transcription assays indicated that ING proteins enhanced TR-dependent, T(3)-induced TRβ gene promoter activity. Examination of endogenous T(3)-responsive promoters (TRβ and TH/bZIP) in the tail by chromatin immunoprecipitation assays showed that ING proteins were recruited to TRE-containing regions in T(3)-dependent and independent ways, respectively. Moreover, ING and TR proteins coimmunoprecipitated from tail protein homogenates derived from metamorphic climax animals.We show for the first time that ING proteins modulate TH-dependent responses, thus revealing a novel role for ING proteins in hormone signaling. This has important implications for understanding hormone influenced disease states and suggests that the induction of ING proteins may facilitate TR function during metamorphosis in a tissue-specific manner.http://europepmc.org/articles/PMC3230625?pdf=render
spellingShingle Caren C Helbing
Mary J Wagner
Katherine Pettem
Jill Johnston
Rachel A Heimeier
Nik Veldhoen
Frank R Jirik
Yun-Bo Shi
Leon W Browder
Modulation of thyroid hormone-dependent gene expression in Xenopus laevis by INhibitor of Growth (ING) proteins.
PLoS ONE
title Modulation of thyroid hormone-dependent gene expression in Xenopus laevis by INhibitor of Growth (ING) proteins.
title_full Modulation of thyroid hormone-dependent gene expression in Xenopus laevis by INhibitor of Growth (ING) proteins.
title_fullStr Modulation of thyroid hormone-dependent gene expression in Xenopus laevis by INhibitor of Growth (ING) proteins.
title_full_unstemmed Modulation of thyroid hormone-dependent gene expression in Xenopus laevis by INhibitor of Growth (ING) proteins.
title_short Modulation of thyroid hormone-dependent gene expression in Xenopus laevis by INhibitor of Growth (ING) proteins.
title_sort modulation of thyroid hormone dependent gene expression in xenopus laevis by inhibitor of growth ing proteins
url http://europepmc.org/articles/PMC3230625?pdf=render
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