Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study...

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Autores principales: Cruz Maria Araceli Diaz, Lund Dan, Szekeres Ferenc, Karlsson Sandra, Faresjö Maria, Larsson Dennis
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Lenguaje:EN
Publicado: De Gruyter 2021
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spelling oai:doaj.org-article:d11528fce6834bd588bef5a0b5f6da9c2021-12-05T14:10:54ZCis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems2391-546310.1515/med-2021-0264https://doaj.org/article/d11528fce6834bd588bef5a0b5f6da9c2021-04-01T00:00:00Zhttps://doi.org/10.1515/med-2021-0264https://doaj.org/toc/2391-5463Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through cis-regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation.Cruz Maria Araceli DiazLund DanSzekeres FerencKarlsson SandraFaresjö MariaLarsson DennisDe Gruyterarticleconserved sequencestranscription factor binding sitessplicing sitesnuclear receptor binding domainscrosstalkMedicineRENOpen Medicine, Vol 16, Iss 1, Pp 640-650 (2021)
institution DOAJ
collection DOAJ
language EN
topic conserved sequences
transcription factor binding sites
splicing sites
nuclear receptor binding domains
crosstalk
Medicine
R
spellingShingle conserved sequences
transcription factor binding sites
splicing sites
nuclear receptor binding domains
crosstalk
Medicine
R
Cruz Maria Araceli Diaz
Lund Dan
Szekeres Ferenc
Karlsson Sandra
Faresjö Maria
Larsson Dennis
Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
description Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through cis-regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation.
format article
author Cruz Maria Araceli Diaz
Lund Dan
Szekeres Ferenc
Karlsson Sandra
Faresjö Maria
Larsson Dennis
author_facet Cruz Maria Araceli Diaz
Lund Dan
Szekeres Ferenc
Karlsson Sandra
Faresjö Maria
Larsson Dennis
author_sort Cruz Maria Araceli Diaz
title Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
title_short Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
title_full Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
title_fullStr Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
title_full_unstemmed Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
title_sort cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
publisher De Gruyter
publishDate 2021
url https://doaj.org/article/d11528fce6834bd588bef5a0b5f6da9c
work_keys_str_mv AT cruzmariaaracelidiaz cisregulatoryelementsinconservednoncodingsequencesofnuclearreceptorgenesindicateforcrosstalkbetweenendocrinesystems
AT lunddan cisregulatoryelementsinconservednoncodingsequencesofnuclearreceptorgenesindicateforcrosstalkbetweenendocrinesystems
AT szekeresferenc cisregulatoryelementsinconservednoncodingsequencesofnuclearreceptorgenesindicateforcrosstalkbetweenendocrinesystems
AT karlssonsandra cisregulatoryelementsinconservednoncodingsequencesofnuclearreceptorgenesindicateforcrosstalkbetweenendocrinesystems
AT faresjomaria cisregulatoryelementsinconservednoncodingsequencesofnuclearreceptorgenesindicateforcrosstalkbetweenendocrinesystems
AT larssondennis cisregulatoryelementsinconservednoncodingsequencesofnuclearreceptorgenesindicateforcrosstalkbetweenendocrinesystems
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