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Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate

BACKGROUND: The human Sex Hormone Binding Globulin (SHBG) gene, located at 17p13.1, comprises, at least, two different transcription units regulated by two different promoters. The first transcription unit begins with the exon 1 sequence and is responsible for the production of plasma SHBG by the he...

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Autores principales: Pinós, Tomàs, Barbosa-Desongles, Anna, Hurtado, Antoni, Santamaria-Martínez, Albert, de Torres, Inés, Morote, Joan, Reventós, Jaume, Munell, Francina
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706245/
https://www.ncbi.nlm.nih.gov/pubmed/19534810
http://dx.doi.org/10.1186/1471-2199-10-59
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author Pinós, Tomàs
Barbosa-Desongles, Anna
Hurtado, Antoni
Santamaria-Martínez, Albert
de Torres, Inés
Morote, Joan
Reventós, Jaume
Munell, Francina
author_facet Pinós, Tomàs
Barbosa-Desongles, Anna
Hurtado, Antoni
Santamaria-Martínez, Albert
de Torres, Inés
Morote, Joan
Reventós, Jaume
Munell, Francina
author_sort Pinós, Tomàs
collection PubMed
description BACKGROUND: The human Sex Hormone Binding Globulin (SHBG) gene, located at 17p13.1, comprises, at least, two different transcription units regulated by two different promoters. The first transcription unit begins with the exon 1 sequence and is responsible for the production of plasma SHBG by the hepatocytes, while the second begins with an alternative exon 1 sequence, which replaces the exon 1 present in liver transcripts. Alternative exon 1 transcription and translation has only been demonstrated in the testis of transgenic mice containing an 11-kb human SHBG transgene and in the human testis. Our goal has been to further characterize the 5' end of the SHBG gene and analyze the presence of the SHBG alternative transcripts in human prostate tissue and derived cell lines. RESULTS: Using a combination of in silico and in vitro studies, we have demonstrated that the SHBG gene, along with exon 1 and alternative exon 1 (renamed here exon 1A), contains four additional alternative first exons: the novel exons 1B, 1C, and 1E, and a previously identified exon 1N, which has been further characterized and renamed as exon 1D. We have shown that these four alternative first exons are all spliced to the same 3' splice site of SHBG exon 2, and that exon 1A and the novel exon 1B can be spliced to exon 1. We have also demonstrated the presence of SHBG transcripts beginning with exons 1B, 1C and 1D in prostate tissues and cell lines, as well as in several non-prostatic cell lines. Finally, the alignment of the SHBG mammalian sequences revealed that, while exons 1C, 1D and 1E are very well conserved phylogenetically through non-primate mammal species, exon 1B probably aroused in apes due to a single nucleotide change that generated a new 5' splice site in exon 1B. CONCLUSION: The identification of multiple transcription start sites (TSS) upstream of the annotated first exon of human SHBG, and the detection of the alternative transcripts in human prostate, concur with the prediction of the ENCODE (ENCyclopedia of DNA Elements) project, and suggest that the regulation of SHBG is much more complex than previously reported.
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spelling pubmed-27062452009-07-07 Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate Pinós, Tomàs Barbosa-Desongles, Anna Hurtado, Antoni Santamaria-Martínez, Albert de Torres, Inés Morote, Joan Reventós, Jaume Munell, Francina BMC Mol Biol Research Article BACKGROUND: The human Sex Hormone Binding Globulin (SHBG) gene, located at 17p13.1, comprises, at least, two different transcription units regulated by two different promoters. The first transcription unit begins with the exon 1 sequence and is responsible for the production of plasma SHBG by the hepatocytes, while the second begins with an alternative exon 1 sequence, which replaces the exon 1 present in liver transcripts. Alternative exon 1 transcription and translation has only been demonstrated in the testis of transgenic mice containing an 11-kb human SHBG transgene and in the human testis. Our goal has been to further characterize the 5' end of the SHBG gene and analyze the presence of the SHBG alternative transcripts in human prostate tissue and derived cell lines. RESULTS: Using a combination of in silico and in vitro studies, we have demonstrated that the SHBG gene, along with exon 1 and alternative exon 1 (renamed here exon 1A), contains four additional alternative first exons: the novel exons 1B, 1C, and 1E, and a previously identified exon 1N, which has been further characterized and renamed as exon 1D. We have shown that these four alternative first exons are all spliced to the same 3' splice site of SHBG exon 2, and that exon 1A and the novel exon 1B can be spliced to exon 1. We have also demonstrated the presence of SHBG transcripts beginning with exons 1B, 1C and 1D in prostate tissues and cell lines, as well as in several non-prostatic cell lines. Finally, the alignment of the SHBG mammalian sequences revealed that, while exons 1C, 1D and 1E are very well conserved phylogenetically through non-primate mammal species, exon 1B probably aroused in apes due to a single nucleotide change that generated a new 5' splice site in exon 1B. CONCLUSION: The identification of multiple transcription start sites (TSS) upstream of the annotated first exon of human SHBG, and the detection of the alternative transcripts in human prostate, concur with the prediction of the ENCODE (ENCyclopedia of DNA Elements) project, and suggest that the regulation of SHBG is much more complex than previously reported. BioMed Central 2009-06-17 /pmc/articles/PMC2706245/ /pubmed/19534810 http://dx.doi.org/10.1186/1471-2199-10-59 Text en Copyright © 2009 Pinós et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Pinós, Tomàs
Barbosa-Desongles, Anna
Hurtado, Antoni
Santamaria-Martínez, Albert
de Torres, Inés
Morote, Joan
Reventós, Jaume
Munell, Francina
Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate
title Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate
title_full Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate
title_fullStr Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate
title_full_unstemmed Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate
title_short Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate
title_sort identification, characterization and expression of novel sex hormone binding globulin alternative first exons in the human prostate
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706245/
https://www.ncbi.nlm.nih.gov/pubmed/19534810
http://dx.doi.org/10.1186/1471-2199-10-59
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