Chromatin occupancy by TRα1 in C17.2/TRα1 cells.

*<p>Identified using NUBISCAN. Bold characters correspond to TREs with more that 2-fold enrichment after C17.2/TRα1 cells ChAP. ND: not determined, N/A: not relevant. Mean ± SD for three independent experiments.</p

Kinetics of T3 target genes expression in wild-type and <i>TRα^AMI/S</i> mice in the cerebellum as measured by Q-RT-PCR.

<p>Expression levels were calculated for each target gene by Q-RT-PCR in wild-type and <i>TRα^AMI/S</i> littermates at P4, P8, P15 and P21 (minimum 3 animals of each genotype for each time point). Data are expressed as mean ± SD using wild-type P4 values (A), for genes with decreasing or stable expression levels over time or P21 (B), for genes with increasing expression levels, as a reference for each genotype. *p<0.05; **p<0.01 for comparisons between wild-type and <i>TRα^AMI/S</i> mice for each time point (Student’s t-test).</p

Transfection of TRα1 into C17.2 cells restores their response to T3 treatment.

<p>A. T3-induced <i>Hr</i> expression is detected earlier and stronger in transfected C17.2/TRα1 cells (black bars) than in non-transfected cells (white bars), *p<0.05, Student’s t-test difference between non-transfected cells and C17.2/TRα1 cells. B. The level of change in expression induced by T3 and measured by Q-RT-PCR in C17.2/TRα1 cells is indicated for each target gene, using non-treated cultures as reference (represented as log2 of the fold change). White bars indicate T3 treatment in proliferative medium (containing serum), black bars indicated T3 treatment in serum-deprived medium allowing for differentiation. Most genes show a response only in serum-deprived medium, *p<0.05, Student’s t-test, difference between serum containing and serum deprived cultures.</p

Database analysis of expression patterns and gene functions.

<p>Abbreviations: AS: Astrocytes, BC: Basket cells, BG: Bergmann glia, EGL: external granular layer, GI: Golgi interneurons, IGL: internal granular layer, ML: molecular layer, OL:Oligodendrocytes, PC: Purkinje cells, PCL: Purkinje cell layer, SC: Stellate cells, Ubi: ubiquitous, WM: White matter. N/A: not available. First location is the principal location. Data from Allen Brain Atlas, GENSAT and reference <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030703#pone.0030703-Doyle1" target="_blank">[32]</a>.</p

Cell autonomous effect of <i>in vivo</i> expression of a dominant negative TRα1 mutation.

<p><i>TRα^AMI/S</i> data are reported from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030703#pone-0030703-g002" target="_blank">figure 2</a> for comparisons. ND: Not determined. Values are indicated as mean ± SD. Significant changes (Student T-test) are indicated in bold:</p>**<p>: p<0.01,</p>*<p>: p<0.05.</p

Q-RT-PCR confirmation of T3 mediated regulation in primary cultures of cerebellum neuronal cells.

<p>Bold characters outline fold changes superior to 2.</p

Recovery of known regulatory relations from <i>Regulatory Circuits</i> networks.

Number of relations present in the different relations databases (Cytreg, HTRI, Signor, Tfacts or Trrust) present in the computed networks. Overall, Regulatory Circuits is enriched in relations found in databases, with significant enrichment obtained in 19 out of 20 cases (p-values ranging from 4.6e-3 to 1.7e-290). Relative to Fig 3. (PDF)</p

RDF data structure model after integration of all pre-processed input data.

Example of the data structure obtained after applying Semantic Web technologies integration to B cells genomic datasets. Relative to Fig 1, Results subsection The Regulus tool and Methods subsection Data graph for integration and query. (PDF)</p

SPARQL query used to retrieve all relations between TF, Region and Gene entities and their associated activity patterns.

Relative to Fig 1, Results subsection The Regulus tool and Methods subsection Data graph for integration and query. (PDF)</p

Toy-example of Regulus pipeline.

Top panel: the pool of entities is composed of 2 TFs, 2 regions and 2 genes. All of the biological entities activities or expression are first discretized (see Methods subsection Gene expression and region accessibility patterns). Middle panel: the interactions between the entities are then computed thanks to their inter-dependency and relations, using a Semantic Web framework. Region2 includes no binding site for TF2 therefore this interaction is discarded and Region1 is more than 500kb away from G2 and does not pass the distance threshold. Then, TF-region and region-gene relations are combined to obtain TF-region-gene relations resulting in a putative unsigned network. Bottom panel: relations are then filtered using the likelihood constraints. For each pair of TF expression and region accessibility patterns, the gene expression pattern is compared to the unique “perfect” gene expression pattern compatible either with an activation or an inhibition (see Methods subsection Regulatory likelihood constraints). To include some flexibility in the regulatory relations caused by modulation in TF expression or region accessibility, a relaxation parameter (δ) is introduced. Here the maximum allowed deviation (δ) from a perfect TF expression, gene expression and region accessibility patterns triple is 1. This step attributes a sign to the relation as an activation (+) or an inhibition (-). The result is a filtered and signed network (bottom right box). (PDF)</p