Transcriptional activation of TINF2, a gene encoding the telomere-associated protein TIN2, by Sp1 and NF-κB factors.

The expression of the telomere-associated protein TIN2 has been shown to be essential for early embryonic development in mice and for development of a variety of human malignancies. Recently, germ-line mutations in TINF2, which encodes for the TIN2 protein, have been identified in a number of patien...

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Autores principales:	Zhong-Tao Xin, Kathryn A Carroll, Naveen Kumar, Kui Song, Hinh Ly
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ee32f92c83b34d19a10d2712a4a10126
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spelling	oai:doaj.org-article:ee32f92c83b34d19a10d2712a4a101262021-11-18T06:51:27ZTranscriptional activation of TINF2, a gene encoding the telomere-associated protein TIN2, by Sp1 and NF-κB factors.1932-620310.1371/journal.pone.0021333https://doaj.org/article/ee32f92c83b34d19a10d2712a4a101262011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21731707/?tool=EBIhttps://doaj.org/toc/1932-6203The expression of the telomere-associated protein TIN2 has been shown to be essential for early embryonic development in mice and for development of a variety of human malignancies. Recently, germ-line mutations in TINF2, which encodes for the TIN2 protein, have been identified in a number of patients with bone-marrow failure syndromes. Yet, the molecular mechanisms that regulate TINF2 expression are largely unknown. To elucidate the mechanisms involved in human TINF2 regulation, we cloned a 2.7 kb genomic DNA fragment containing the putative promoter region and, through deletion analysis, identified a 406 bp region that functions as a minimal promoter. This promoter proximal region is predicted to contain several putative Sp1 and NF-κB binding sites based on bioinformatic analysis. Direct binding of the Sp1 and NF-κB transcription factors to the TIN2 promoter sequence was demonstrated by electrophoretic mobility shift assay (EMSA) and/or chromatin immunoprecipitation (ChIP) assays. Transfection of a plasmid carrying the Sp1 transcription factor into Sp-deficient SL2 cells strongly activated TIN2 promoter-driven luciferase reporter expression. Similarly, the NF-κB molecules p50 and p65 were found to strongly activate luciferase expression in NF-κB knockout MEFs. Mutating the predicted transcription factor binding sites effectively reduced TIN2 promoter activity. Various known chemical inhibitors of Sp1 and NF-κB could also strongly inhibit TIN2 transcriptional activity. Collectively, our results demonstrate the important roles that Sp1 and NF-κB play in regulating the expression of the human telomere-binding protein TIN2, which can shed important light on its possible role in causing various forms of human diseases and cancers.Zhong-Tao XinKathryn A CarrollNaveen KumarKui SongHinh LyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 6, p e21333 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhong-Tao Xin Kathryn A Carroll Naveen Kumar Kui Song Hinh Ly Transcriptional activation of TINF2, a gene encoding the telomere-associated protein TIN2, by Sp1 and NF-κB factors.
description	The expression of the telomere-associated protein TIN2 has been shown to be essential for early embryonic development in mice and for development of a variety of human malignancies. Recently, germ-line mutations in TINF2, which encodes for the TIN2 protein, have been identified in a number of patients with bone-marrow failure syndromes. Yet, the molecular mechanisms that regulate TINF2 expression are largely unknown. To elucidate the mechanisms involved in human TINF2 regulation, we cloned a 2.7 kb genomic DNA fragment containing the putative promoter region and, through deletion analysis, identified a 406 bp region that functions as a minimal promoter. This promoter proximal region is predicted to contain several putative Sp1 and NF-κB binding sites based on bioinformatic analysis. Direct binding of the Sp1 and NF-κB transcription factors to the TIN2 promoter sequence was demonstrated by electrophoretic mobility shift assay (EMSA) and/or chromatin immunoprecipitation (ChIP) assays. Transfection of a plasmid carrying the Sp1 transcription factor into Sp-deficient SL2 cells strongly activated TIN2 promoter-driven luciferase reporter expression. Similarly, the NF-κB molecules p50 and p65 were found to strongly activate luciferase expression in NF-κB knockout MEFs. Mutating the predicted transcription factor binding sites effectively reduced TIN2 promoter activity. Various known chemical inhibitors of Sp1 and NF-κB could also strongly inhibit TIN2 transcriptional activity. Collectively, our results demonstrate the important roles that Sp1 and NF-κB play in regulating the expression of the human telomere-binding protein TIN2, which can shed important light on its possible role in causing various forms of human diseases and cancers.
format	article
author	Zhong-Tao Xin Kathryn A Carroll Naveen Kumar Kui Song Hinh Ly
author_facet	Zhong-Tao Xin Kathryn A Carroll Naveen Kumar Kui Song Hinh Ly
author_sort	Zhong-Tao Xin
title	Transcriptional activation of TINF2, a gene encoding the telomere-associated protein TIN2, by Sp1 and NF-κB factors.
title_short	Transcriptional activation of TINF2, a gene encoding the telomere-associated protein TIN2, by Sp1 and NF-κB factors.
title_full	Transcriptional activation of TINF2, a gene encoding the telomere-associated protein TIN2, by Sp1 and NF-κB factors.
title_fullStr	Transcriptional activation of TINF2, a gene encoding the telomere-associated protein TIN2, by Sp1 and NF-κB factors.
title_full_unstemmed	Transcriptional activation of TINF2, a gene encoding the telomere-associated protein TIN2, by Sp1 and NF-κB factors.
title_sort	transcriptional activation of tinf2, a gene encoding the telomere-associated protein tin2, by sp1 and nf-κb factors.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/ee32f92c83b34d19a10d2712a4a10126
work_keys_str_mv	AT zhongtaoxin transcriptionalactivationoftinf2ageneencodingthetelomereassociatedproteintin2bysp1andnfkbfactors AT kathrynacarroll transcriptionalactivationoftinf2ageneencodingthetelomereassociatedproteintin2bysp1andnfkbfactors AT naveenkumar transcriptionalactivationoftinf2ageneencodingthetelomereassociatedproteintin2bysp1andnfkbfactors AT kuisong transcriptionalactivationoftinf2ageneencodingthetelomereassociatedproteintin2bysp1andnfkbfactors AT hinhly transcriptionalactivationoftinf2ageneencodingthetelomereassociatedproteintin2bysp1andnfkbfactors
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Transcriptional activation of TINF2, a gene encoding the telomere-associated protein TIN2, by Sp1 and NF-κB factors.

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