Picture from Tepper RG et al. (2013) Cell "PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated ...."

(F-H) DAF-16 becomes more cytoplasmic with age, and nuclear localization of PQM-1::GFP decreases significantly with age. Data are represented as mean +/- SEM (G and H).

Picture from Tepper RG et al. (2013) Cell "PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated ...."

A promoter-GFP construct of a PQM-1-regulated class II gene, F55G11.2, that containsa DAE motif in its promoter is abundantly expressed in the intestine of wild type worms.

Picture from Tepper RG et al. (2013) Cell "PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated ...."

Figure 2. PQM-1 Is the DAE-Binding Factor (A) Fold enrichment over random expectation of DBE affinity in sequences bound by each of the 46 transcription factors assayed by the modENCODE consortium using ChIP-seq (Niu et al., 2011); the last stage assayed was analyzed. Shown are the 13 most highly enriched factors (p < 10-16 in each case; see Extended Experimental Procedures). As expected, the highest enrichment is found in DAF-16-bound regions. (B) Same as (A), but for DAE affinity. The latter is strikingly enriched within sequences bound by PQM-1. (C) Distribution of ChIP-seq binding site centers relative to transcriptional start sites, based on all modENCODE ChIP-seq data (Niu et al., 2011). (D) PQM-1-binding sites are significantly enriched upstream of both class I and class II genes, with the strongest effect for class II. (E) PQM-1 targets are predicted to primarily be intestinally expressed, and depleted in neurons. (F) Both class I and class II genes are specifically downregulated in the pqm-1 mutant relative to wild-type. (G-J) A promoter-GFP construct of a PQM-1-regulated class II gene, F55G11.2, that containsa DAE motif in its promoter is abundantly expressed in the intestine of wild type worms, but its expression isdecreased in the pqm-1(-)background (p<0.0001, Student's t test for unpaired samples), when the DAE is mutated (p<0.001) (H, I, J), and in a daf-2 background (I and J), and is increased in a daf-18/PTEN background in a DAE-dependent manner (J). Data are represented as mean +/- SEM (H, I, and J).

Picture from McCarroll SA et al. (2005) Curr Biol "Identification of transcriptional regulatory elements in chemosensory ...."

(B) srh-132::GFP transgene expressed in ADL neuron. This transgene is also expressed in the head mesodermal cell (not shown). Anterior is at left, and ventral is down. Arrowheads denote characteristic anterior extension of the ADL axon from the cell body. The sensory axons extend a short distance to the nerve ring. The dendrites of all sensory neurons extend anteriorly. Autofluorescence of the gut is visible.

Picture from McCarroll SA et al. (2005) Curr Biol "Identification of transcriptional regulatory elements in chemosensory ...."

Figure 3. Expression of Transgenes with the Extended E-Box ADL Motif. (A) sri-51::GFP transgene expressed in ADL neuron.(B) srh-132::GFP transgene expressed in ADL neuron. This transgene is also expressed in the head mesodermal cell (not shown).(C) odr-10::GFP transgene expressed in AWA neuron.(D) odr-10(+ADL motif)::GFP transgene expressed in ADL neuron. Anterior is at left, and ventral is down. Arrowheads denote characteristic anterior extension of the ADL axon (A, B, and D) and ventral extension of the AWA axon (C) from the cell body. The sensory axons extend a short distance to the nerve ring. The dendrites of all sensory neurons extend anteriorly. Autofluorescence of the gut is visible in (B), (C), and (D).

Picture from Tepper RG et al. (2013) Cell "PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated ...."

Figure 6. PQM-1 Is a Major Regulator of Age-Related Loss of Gene Expression (A) The distribution of genes classified by Budovskaya et al. (2008) as 'age-regulated' versus our ranking shows that our classes I and II are both strongly affected during normal aging. (B) Differential expression of all genes between day 11 and day 2 of adulthood, shown in the context of our ranking. (C) Expression change (mean log ratio) for class I, class II, and other genes as a function of age, day 2 of adulthood being the reference. (D) Fold enrichment versus genome-wide average of ChIP-seq binding sites in the 1% of genes most strongly downregulated with age. (E) Average expression of regulons (sets of targets genes as defined based on ChIP-seq data) for various transcription factors assayed by Niu et al. (2011), shown as a function of advancing age. (F-H) DAF-16 becomes more cytoplasmic with age, and nuclear localization of PQM-1::GFP decreases significantly with age. Data are represented as mean +/- SEM (G and H).