Gene Expression Is Driven by Context: The Mouse Gelsolin Multiple Promoters

<div><p>(A) Map of various isoforms of gelsolin mRNAs on the genome. There are three main TSSs, indicated by blue circles. The numbers are the arbitrary expression cluster numbers (clusters 66, 39, and 45) where these TSSs were assigned. The two upstream promoters produce RNAs that encode for the cytoplasmic isoform, while the third main promoter (cluster 45) encodes an mRNA that produces the secreted isoform of gelsolin.</p> <p>(B–D) The expression context of the three promoters is different. The <i>x-</i>axis shows different tissues based on their transcriptional similarity, and the <i>y-</i>axis shows TSS clustering. Various forms of gelsolin are expressed in different transcriptional contexts, emphasizing the importance of distinguishing between promoters and isoforms in the expression analysis.</p></div

Overview of probe design: genomic coordination of TSSs and CAGE-TSSchip probes

<p><b>Copyright information:</b></p><p>Taken from "CAGE-TSSchip: promoter-based expression profiling using the 5'-leading label of capped transcripts"</p><p>http://genomebiology.com/2007/8/3/R42</p><p>Genome Biology 2007;8(3):R42-R42.</p><p>Published online 26 Mar 2007</p><p>PMCID:PMC1868931.</p><p></p> The upper four tracks are an arrangement example of full-length transcripts (cDNA) and 5'-ends of transcripts derived from various methods (cap analysis gene expression [CAGE], 5'-expressed sequence tag [EST], and 5'-end of gene identification signature/gene signature cloning [4]). Tag clusters (TC; green arrow) are the overlapping regions of the 5'-ends. The most frequent transciption start site (TSS) for each TC is the representative position (vertical line from TC arrows). Fragments for the probe design, of 120-nucleotide long genomic sequences, starts from the representative position of each TC fragment, shown by cyan arrows. If the fragment overlaps the 5'-end of any exon-intron junction (diamond of cDNA and 5'-EST transcripts), the fragment skips the intron to the next exon. According to the Agilent probe design service, the 60-nucleotide appropriate region within each fragment would then be suggested for array probes (probe; blue arrows). Details of probe preparation are available in Additional data file 8

Micro-Insertion and -Deletion Rates

<div><p>Promoter rates calculated as insertion (blue) and deletion (red) events per nucleotide in 100-bp consecutive windows (<i>x-</i>axis). Error bars show 95% confidence intervals; solid horizontal lines show rates calculated from AR alignments. Vertical grey line indicates the +1 TSS position.</p> <p>(A) Human rates based on alignments between human, chimpanzee, and macaque; rates shown are derived only from the human terminal branch (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020030#s3" target="_blank">Materials and Methods</a>).</p> <p>(B) Mouse terminal branch rates based on comparisons between mouse, rat, and dog.</p></div

Comparison of the Expression Patterns between Somatosensory Cortex and Liver

<p>The upper panel shows the expression pattern on Chromosome 19, bases 28,000,001 to 28,500,000, in somatosensory cortex. The lower panel shows the expression pattern of the same region in liver. The two ellipses show the expression patterns of the regions encoding the <i>Slc1a1</i> gene and <i>mmu-mir-101b</i> miRNA (embedded in the intron of <i>Rcl1</i>). C, comparatively expressed; N, not expressed; S, strongly expressed; W, weakly expressed.</p

Genomic Expression Patterns for Chromosome 11 in Muscle and Chromosome 7 in Prostate Gland

<p>Expression pattern of Chromosome 11 in muscle, bases 66,783,001 to 66,932,000 (above), and Chromosome 7 in prostate gland, bases 17,036,001 to 17,210,000 (below). The upward and downward bars from N indicate the expression levels of the forward and reverse strands at the block, respectively. The genomic positional expression patterns of the two regions showed high similarity.</p

Patterns of Evolution in Promoter Subcategories

<div><p>(A) The percentage of all mouse TSSs assigned to each category. Dark blue shows the percentage assigned to the category annotated to the left, and light blue the reciprocal category (e.g., non-CpG is the reciprocal of CpG). The colour coding is consistent with (B–E). The “map” category refers to whether the TSS could be mapped to the annotated 5′-most end of a known protein-coding gene (dark blue), could not mapped to a gene (light blue), or maps internally to an annotated gene extent (grey). See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020030#s3" target="_blank">Materials and Methods</a> for details of category assignment.</p> <p>(B–E) Single nucleotide resolution estimates of substitution rates calculated from promoters assigned to the indicated categories. Only rates calculated from mouse–dog comparisons are shown. The 95% confidence intervals have been excluded for clarity. Red horizontal lines show <i>K</i> for ARs, nucleotide position is shown on the <i>x-</i>axis relative to the TSS at +1 (grey vertical line), and <i>K</i> is shown on the <i>y-</i>axis. Although there are three categories indicated for gene mapping in (A), only two are shown for clarity.</p></div

Genomic Expression Pattern and Sequence Similarity for Chromosome 11 in Muscle and Chromosome 7 in Prostate Gland

<p>Sequence similarity is shown for the same regions as in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020044#pgen-0020044-g002" target="_blank">Figure 2</a>. Expression patterns for Chromosome 11 in muscle and Chromosome 7 in prostate gland are shown at the right and at the top, respectively. The dot matrix shows the low sequence similarity of the two regions.</p

High-Resolution Pairwise Substitution Rate Estimates <i>(K)</i> across Promoter Region Alignments

<div><p>The <i>x-</i>axis denotes nucleotide position relative to the TSS reference position at +1 (grey vertical line). Error bars (lighter shading) show 95% confidence intervals for each data point.</p> <p>(A) Rates calculated from mouse-based alignments.</p> <p>(B) Rates calculated from human-based alignments.</p></div

Genomic Expression Pattern for Chromosome 5, Bases 134,880,800 to 134,943,900, in Macrophage

<p>This region on Chromosome 5 shows similarity of expression pattern between the forward (TU 81377; <i>Perq1</i>) and reverse strands (TU 151094; <i>Gnb2</i>). The region from base 134,908,626 to base 134,893,818 (“known S-AS”) was reported by SADB as an overlapping region of sense–antisense transcription.</p

The Distribution of Observed Scores and the Extreme Value Distribution

<p>The bars show the distribution of observed scores, and the line indicates an extreme value distribution. The horizontal axis shows the score, and the vertical axis shows the frequency of the score.</p