Transcriptomine, a web resource for nuclear receptor signaling transcriptomes

Abstract

The nuclear receptor (NR) superfamily of ligand-regulated transcription factors directs ligand- and tissue-specific transcriptomes in myriad developmental, metabolic, immunological, and reproductive processes. The NR signaling field has generated a wealth of genome-wide expression data points, but due to deficits in their accessibility, annotation, and integration, the full potential of these studies has not yet been realized. We searched public gene expression databases and MEDLINE for global transcriptomic datasets relevant to NRs, their ligands, and coregulators. We carried out extensive, deep reannotation of the datasets using controlled vocabularies for RNA Source and regulating molecule and resolved disparate gene identifiers to official gene symbols to facilitate comparison of fold changes and their significance across multiple datasets. We assembled these data points into a database, Transcriptomine (http://www.nursa.org/transcriptomine), that allows for multiple, menu-driven querying strategies of this transcriptomic "superdataset," including single and multiple genes, Gene Ontology terms, disease terms, and uploaded custom gene lists. Experimental variables such as regulating molecule, RNA Source, as well as fold-change and P value cutoff values can be modified, and full data records can be either browsed or downloaded for downstream analysis. We demonstrate the utility of Transcriptomine as a hypothesis generation and validation tool using in silico and experimental use cases. Our resource empowers users to instantly and routinely mine the collective biology of millions of previously disparate transcriptomic data points. By incorporating future transcriptome-wide datasets in the NR signaling field, we anticipate Transcriptomine developing into a powerful resource for the NR- and other signal transduction research communities.

NURBS: a database of experimental and predicted nuclear receptor binding sites of mouse

“…Other existing NR databases are devoted to the sequences, structures and functions (Martinez et al, 1998), mutations (Van Durme et al, 2003;Vroling et al, 2012) and phylogenies (Ruau et al, 2004) of NRs, not their binding sites. Recently, Ochsner et al (2012) set-up a database, Transcriptomine, which is focused on the expression and function of NRs-related genes. The well developed Cistrome (Tang et al, 2011) provides information about a number of NRs and their co-factors and epigenomic information, and it is better suited for investigating individual NR, as it does not provide features for comparison between NRs.…”

Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice

“…Written informed consent was obtained from all individuals and/or from parents and approved by the ''Comité de Protection des Personnes pour la Recherche Biomédicale Ile de France II.'' In two of these families, we identified heterozygous loss-of-function mutations in GREB1L (growth regulation by estrogen in breast cancer 1-like; GenBank: NM_001142966.2), a gene reported as a target of retinoic acid signaling 13 ( Figure 1, Table 1). In family 1, analyzed by combined WES and linkage analysis (Table S1), we identified a single base pair deletion (c.1582delC) leading to a frameshift (p.Gln528Argfs*12) in the two fetuses affected with BKA (II-3 and II-4 in Figure 1A) and their alive brother (II-2) Mutations identified in BKA-affected case subjects are indicated in bold and the mutation that appeared de novo in a mother in italics.…”

“…22,23 GREB1L has been reported as a target of retinoic acid signaling, a pathway that is crucial for renal development and the dysregulation of which has been proposed as a causative mechanism for urinary tract malformations. 13,[24][25][26] The recent identification of GREB1L mutations in two families with renal agenesis 27 highlighted this gene as a major actor of kidney differentiation. In order to characterize the pattern of GREB1L expression, we first used cDNA panels from various human fetal and adult tissues.…”

Gonadal Steroid Action

“…TMPRSS2 has been shown to be robustly induced by AR 97,98 and is downregulated in androgen-independent prostate tumors, and a fusion of the TMPRSS2 gene with the erythroblast transformationspecific (ETS)-related gene, a member of the ETS family of transcription factors, is one of the best characterized genetic lesions in prostate cancer. TMPRSS2 has been shown to be robustly induced by AR 97,98 and is downregulated in androgen-independent prostate tumors, and a fusion of the TMPRSS2 gene with the erythroblast transformationspecific (ETS)-related gene, a member of the ETS family of transcription factors, is one of the best characterized genetic lesions in prostate cancer.…”

“…TMPRSS2 has been shown to be robustly induced by AR 97,98 and is downregulated in androgen-independent prostate tumors, and a fusion of the TMPRSS2 gene with the erythroblast transformationspecific (ETS)-related gene, a member of the ETS family of transcription factors, is one of the best characterized genetic lesions in prostate cancer. 97,98 Members of the ADAMTS family share several distinct protein modules, including propeptide, metalloproteinase, and disintegrin-like domains and a thrombospondin type 1 (TS) motif. Along with HSP90 and HSP23, FKBP5 has been shown to interact functionally with mature heterooligomeric PGR in the absence of their ligand, hinting at a role for mutual antagonism between AR and PGR in the regulation of their respective target gene networks.…”