Abstract
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.
Highlights
The nuclear receptor superfamily (NRS) is composed of ligand-activated transcription factors that control important developmental and physiological processes, by regulating gene expression when bound to specific DNA sequences
Our results show that conserved NRS intronic sequences are more abundant in the first than other introns, are enriched with transcription factor binding sites (TFBS), and contain SS, which are often co-localized with TFBS
Several transcription factor binding domain (TFBD) families for TFBS were found in intron sequences, some of which contained specific TFBS for nuclear receptors (NRs) and p53
Summary
The nuclear receptor superfamily (NRS) is composed of ligand-activated transcription factors that control important developmental and physiological processes, by regulating gene expression when bound to specific DNA sequences. Introns are a major proportion of DNA in both the plant and mammalian genome and are considered relevant components for genome adaptation [4]. They are not removed after RNA processing and are responsible for chromatin modification, transcription, RNA splicing, editing, translation, and gene expression [4,5,6,7]. The presence of introns elevates gene expression in a wide range of organisms including mammals [6,8,9]. Even in the absence of the promoter in some genes, mRNA accumulation can be stimulated by the presence of certain regulatory intronic sequences [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
