Histone modifications associated with fragment sequences^a.

a<p>“liver” signifies histone modifications associated with fragment in HepG2 cells; “other” signifies histone modifications in cell types other than HepG2.</p>b<p>No histone modification data for mitochondrial DNA.</p

Regulatory activity of putative elements.

<p>(<b>A</b>) Mean activities of 8 replicates of Sau3AI-digested putative regulatory elements in C3A liver cells. Log₁₀ changes relative to promoter-only construct shown. Error bars, standard error of the mean. (**, P<0.01 and ***, P<0.0001 compared to promoter-only construct, both figures.) (<b>B</b>) Mean activities of 8 replicates of AluI-digested putative regulatory elements in C3A liver cells.</p

Distributions and workflow.

<p>(<b>A</b>) Quantile normalized relative luciferase activity for Sau3AI-digested exonic fragments in liver C3A cells compared within, and between, plates. Relative luciferase activity is the log₁₀ ratio of firefly luciferase to <i>Renilla</i> luciferase. Batch number indicates corresponding 96-well plate. (<b>B</b>) Quantile normalized relative luciferase activity for AluI-digested exonic fragments in C3A liver cells. (<b>C</b>) Distribution of relative luciferase activities for Sau3aI-digested fragments in liver C3A cells. (<b>D</b>) Distribution of relative luciferase activities for AluI-digested fragments in liver C3A cells. (<b>E</b>) Workflow for identifying regulatory elements.</p

Discovery and Characterization of Human Exonic Transcriptional Regulatory Elements

<div><p>We sought exonic transcriptional regulatory elements by shotgun cloning human cDNA fragments into luciferase reporter vectors and measuring the resulting expression levels in liver cells. We uncovered seven regulatory elements within coding regions and three within 3' untranslated regions (UTRs). Two of the putative regulatory elements were enhancers and eight were silencers. The regulatory elements were generally but not consistently evolutionarily conserved and also showed a trend toward decreased population diversity. Furthermore, the exonic regulatory elements were enriched in known transcription factor binding sites (TFBSs) and were associated with several histone modifications and transcriptionally relevant chromatin. Evidence was obtained for bidirectional <em>cis-</em>regulation of a coding region element within a tubulin gene, TUBA1B, by the transcription factors PPARA and RORA. We estimate that hundreds of exonic transcriptional regulatory elements exist, an unexpected finding that highlights a surprising multi-functionality of sequences in the human genome.</p> </div

Genomic locations of exonic regulatory elements.

<p>Positions of fragments within exons, including coding regions (thick boxes) and 3′ UTRs (thin boxes).</p

FileS2_ExpressionQTL

Expression QTL supplementary file, analyzed in "Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes". Data file that includes all identified expression QTL associations. Includes tracking IDs of the feature and SNP, positions, p value of association, SNP odds ratio and weight, SNP distance to gene and interaction type (local or trans)