Gene ontologies, expression in native tissues, and presence of retinoic acid response element (RARE). A.

<p>Enrichment analysis on the 125 candidate target genes showed that they are associated with many biological processes (green box) and diseases (red box), some of which are highly relevant to renal physiology and pathology. Those marked with an asterisk were reported to be associated with tRA/RAR signaling. The full list of gene ontologies for the 125 candidate target genes are in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725.s007" target="_blank">Table S4</a>. <b>B.</b> (<b>i</b>) The 20 validated target genes of endogenous tRA/RARs were reported to be involved in retinol metabolism (A), cell-cell, cell-substrate interaction (B), ureteric bud branching (C), immune/inflammatory processes (D), oxidative stress (E), repair/regeneration (F), ion/solute/water transport and metabolism (G), and gene transcription/translation (H); functions of 9930023K05Rik, Klhdc7a, Sorcs2, and 2310007B03Rik are not yet known. Pink: GeneGO Metacore™, Yellow: DAVID <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Huang1" target="_blank">[50]</a>, Green: GeneGO Metacore™ and DAVID, Blue: additional literature review <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Zeisberg1" target="_blank">[20]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Behr1" target="_blank">[22]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Levashova1" target="_blank">[45]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Starkey1" target="_blank">[48]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Pradervand1" target="_blank">[51]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Bonilla1" target="_blank">[52]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Zhang1" target="_blank">[53]</a>. The full list of gene ontologies for the 20 validate target genes are in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725.s008" target="_blank">Table S5</a>. (<b>ii</b>) Expression of the validated genes in native samples, available through Gene Expression Omnibus datasets (Ω: GSE6290, θ: GSE7891), was reviewed. E11.5 UB: embryonic day 11.5 ureteric bud cells from mice (three samples), E15.5 mCD: embryonic day 15.5 medullary collecting duct cells from mice (three samples), rat IMCD: inner medullary collecting duct cells from rat (one sample from 6-week-old and two samples from 10-week-old). +: present, −: absent, ud: undetermined; ?: present in 6-week-old sample but absent from 10-week-old samples. (<b>iii</b>) The number of direct-repeat 5 (DR5) RARE that are present in the validated genes in whole mouse genome is summarized here, based on report from Lalevee et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045725#pone.0045725-Lalevee1" target="_blank">[4]</a>. *: At least one of the DR5 RAREs is present within 10 kb from transcriptional start site and from gene end.