Publication Date:
2022-05-25
Description:
Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Journal of Steroid Biochemistry and Molecular Biology 184 (2018): 3-10, doi:10.1016/j.jsbmb.2018.02.010.
Description:
Nuclear receptors are a superfamily of transcription factors restricted to animals. These transcription
factors regulate a wide variety of genes with diverse roles in cellular homeostasis, development, and
physiology. The origin and specificity of ligand binding within lineages of nuclear receptors (e.g.,
subfamilies) continues to be a focus of investigation geared toward understanding how the functions of
these proteins were shaped over evolutionary history. Among early-diverging animal lineages, the
retinoid X receptor (RXR) is first detected in the placozoan, Trichoplax adhaerens. To gain insight into
RXR evolution, we characterized ligand- and DNA-binding activity of the RXR from T. adhaerens
(TaRXR). Like bilaterian RXRs, TaRXR specifically bound 9-cis-retinoic acid, which is consistent with a
recently published result and supports a conclusion that the ancestral RXR bound ligand. DNA binding
site specificity of TaRXR was determined through protein binding microarrays (PBMs) and compared
with human RXR. The binding sites for these two RXR proteins were broadly conserved (~85% shared
high-affinity sequences within a targeted array), suggesting evolutionary constraint for the regulation of
downstream genes. We searched for predicted binding motifs of the T. adhaerens genome within 1000
bases of annotated genes to identify potential regulatory targets. We identified 648 unique protein coding
regions with predicted TaRXR binding sites that had diverse predicted functions, with enriched processes
related to intracellular signal transduction and protein transport. Together, our data support hypotheses
that the original RXR protein in animals bound a ligand with structural similarity to 9-cis-retinoic acid;
the DNA motif recognized by RXR has changed little in more than 1 billion years of evolution; and the
suite of processes regulated by this transcription factor diversified early in animal evolution.
Description:
Support for AMT
was provided by the Tropical Research Initiative and an Internal Research and Development Award from
the Woods Hole Oceanographic Institution. AMR was supported by NIH award R15GM114740. JM was
supported by NSF award 1536530 to AMR. DM-P, BF and FMS were supported by NIH award
R01DK094707 to FMS.
Keywords:
DNA binding motif
;
Nuclear receptor
;
Protein binding microarray
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
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