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

Maria Araceli Diaz Cruz1, Dan Lund2, Ferenc Szekeres3

  • 1Research School of Health and Welfare, School of Health and Welfare, Jönköping University, Jönköping, Sweden.

Open Medicine (Warsaw, Poland)
|May 6, 2021
PubMed

Insights

This study reveals genetic crosstalk between steroid nuclear receptors (NRs) in conserved DNA sequences. This finding offers new insights into hormone regulation and potential therapeutic targets for hormone-driven diseases.

Area of Science:

  • Genetics
  • Molecular Biology
  • Endocrinology

Background:

  • Nuclear receptors (NRs) are key regulators of gene expression.
  • Crosstalk among steroid NR systems is implicated in hormone-driven cancers.
  • Genetic-level investigation of steroid NR crosstalk is limited.

Purpose of the Study:

  • To investigate genetic crosstalk between steroid NRs within conserved intron and exon sequences.
  • To focus on NRs relevant to prostate cancer etiology.
  • To identify potential regulatory elements involved in NR interactions.

Main Methods:

  • Evaluated conserved intron and exon sequences across the 49 members of the Nuclear Receptor Superfamily (NRS).
  • Assessed conserved regions for regulatory and NR-binding potential.
  • Analyzed transcription factor binding sites (TFBS) within conserved NRS regions.

Main Results:

  • Higher sequence conservation was observed in the first intron (35%) compared to downstream introns.
  • 79% of conserved NRS regions contained putative TFBS, with a significant fraction including splicing sites (SS).
  • Nuclear receptors (NRs) were identified as transcription factors binding to 5% of intronic TFBS and 16% of exonic TFBS.

Conclusions:

  • Evidence suggests crosstalk between steroid NRs, including vitamin D, estrogen, progesterone, and retinoic acid systems.
  • This crosstalk occurs via cis-regulatory elements within conserved intronic and exonic sequences.
  • The findings provide a basis for novel therapeutic targets in steroid NR regulation.
Keywords:
conserved sequencescrosstalknuclear receptor binding domainssplicing sitestranscription factor binding sites

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