The structure and evolution of<i>cis</i>-regulatory regions: the<i>shavenbaby</i>story

Stern, David L.; Frankel, Nicolás

doi:10.1098/rstb.2013.0028

Cited by 72 publications

(61 citation statements)

References 48 publications

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“…It should be noted however that even if eQTLs are shared, we are not sure whether the causative mutations are shared (Conte, Arnegard, Schluter, & Peichel, ; Rosenblum, Parent, & Brandt, ). As in the case of Drosophila (Stern & Frankel, ), multiple mutations may accumulate at a QTL, indicating that a single QTL does not mean a single mutation.…”

Section: Discussionmentioning

confidence: 99%

Parallel transcriptome evolution in stream threespine sticklebacks

2018

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Natural selection can cause similar phenotypic evolution in phylogenetically independent lineages inhabiting similar environments. Compared to morphological, behavioral, and physiological traits, little is known about the parallel evolution of transcriptome. Furthermore, the relative contribution of cis‐ and trans‐regulatory changes to parallel transcriptome evolution largely remains unclear. The threespine stickleback fish (Gasterosteus aculeatus) is a great model for studying parallel evolution because its ancestral marine populations independently colonized freshwater habitats in multiple geographical regions, resulting in independent pairs of marine and freshwater ecotypes in each region. Here, we investigated transcriptomic parallelism among the marine and stream ecotypes of Japanese and Canadian threespine sticklebacks by conducting common garden experiments and microarray analysis of the brain, which controls several physiological and behavioral traits differing between these ecotypes. We found parallel expression differences in 103 genes, including those encoding the enzymes involved in taurine synthesis and glycoprotein hydrolysis. The number of genes differentially expressed in parallel was significantly larger than the number of genes showing an antiparallel pattern (71 genes). To investigate the genetic architecture underlying transcriptome divergence, we re‐analyzed the previous expression quantitative trait locus (eQTL) data and found that most eQTLs were located on the same chromosome as the transcripts, possibly in cis‐regulatory regions. Furthermore, the effect sizes of the eQTLs on the same chromosomes were larger than those on different chromosomes. Thus, we found that divergence in the brain transcriptome between the ecotypes shows parallelism and is mainly caused by genetic changes occurring on the same chromosome as the target genes.

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Section: Discussionmentioning

confidence: 99%

Parallel transcriptome evolution in stream threespine sticklebacks

2018

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“…Elegant studies have revealed that regulation of Svb controls dorsal and ventral cuticle patterning in drosophilids (reviewed by Delon and Payre, 2004;Stern and Frankel, 2013) through its activation of numerous effector molecules (Chanut-Delalande et al, 2012). Yet whether and how Svb activity might control the row-specific shapes of ventral denticles has been unclear.…”

Section: Discussionmentioning

confidence: 99%

SoxNeuro and shavenbaby act cooperatively to shape denticles in the embryonic epidermis of Drosophila

Rizzo

Bejsovec

2017

Development

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During development, extracellular signals are integrated by cells to induce the transcriptional circuitry that controls morphogenesis. In the fly epidermis, Wingless (Wg)/Wnt signaling directs cells to produce either a distinctly shaped denticle or no denticle, resulting in a segmental pattern of denticle belts separated by smooth, or 'naked', cuticle. Naked cuticle results from Wg repression of shavenbaby (svb), which encodes a transcription factor required for denticle construction. We have discovered that although the svb promoter responds differentially to altered Wg levels, Svb alone cannot produce the morphological diversity of denticles found in wild-type belts. Instead, a second Wg-responsive transcription factor, SoxNeuro (SoxN), cooperates with Svb to shape the denticles. Coexpressing ectopic SoxN with svb rescued diverse denticle morphologies. Conversely, removing SoxN activity eliminated the residual denticles found in svb mutant embryos. Furthermore, several known Svb target genes are also activated by SoxN, and we have discovered two novel target genes of SoxN that are expressed in denticle-producing cells and that are regulated independently of Svb. We conclude that proper denticle morphogenesis requires transcriptional regulation by both SoxN and Svb.

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“…Classical genetics approaches have provided evidence of redundant, additive, and synergistic enhancer relationships at a handful of loci (Banerji et al, 1983; Banerji et al, 1981; Bender et al, 2012; Blasquez et al, 1992; de Villiers and Schaffner, 1981; Fujioka et al, 1999; Fulton and van Ness, 1994; Guo et al, 2012; Hong et al, 2008; Kehayova et al, 2011; Lam et al, 2015; Montavon et al, 2011; Perry et al, 2010; Small et al, 1992; Stern and Frankel, 2013). For example, two enhancers regulating Pomc are both necessary in the mouse embryo, indicating a synergistic relationship, while the enhancers contribute additively to Pomc expression in adult mice (Lam et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Multiplex Enhancer Interference Reveals Collaborative Control of Gene Regulation by Estrogen Receptor α-Bound Enhancers

2017

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Summary Multiple regulatory regions have the potential to regulate a single gene, yet how these elements combine to impact gene expression remains unclear. To uncover the combinatorial relationships between enhancers, we developed Enhancer-interference (Enhancer-i), a CRISPR interference-based approach that uses 2 different repressive domains, KRAB and SID, to prevent enhancer activation simultaneously at multiple regulatory regions. We applied Enhancer-i to promoter-distal estrogen receptor α binding sites (ERBS), which cluster around estradiol-responsive genes and therefore may collaborate to regulate gene expression. Targeting individual sites revealed predominant ERBS that are completely required for the transcriptional response, indicating a lack of redundancy. Simultaneous interference of different ERBS combinations identified supportive ERBS that contribute only when predominant sites are active. Using mathematical modeling, we find strong evidence for collaboration between predominant and supportive ERBS. Overall, our findings expose a complex functional hierarchy of enhancers, where multiple loci bound by the same transcription factor combine to fine tune the expression of target genes.

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The structure and evolution ofcis-regulatory regions: theshavenbabystory

Cited by 72 publications

References 48 publications

Parallel transcriptome evolution in stream threespine sticklebacks

Parallel transcriptome evolution in stream threespine sticklebacks

SoxNeuro and shavenbaby act cooperatively to shape denticles in the embryonic epidermis of Drosophila

Multiplex Enhancer Interference Reveals Collaborative Control of Gene Regulation by Estrogen Receptor α-Bound Enhancers

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