Comparative genomics of gene regulation—conservation and divergence of cis-regulatory information

Meireles-Filho, Antonio C. A.; Stark, Alexander

doi:10.1016/j.gde.2009.10.006

Cited by 78 publications

(50 citation statements)

References 71 publications

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“…5b). Rather than relying on extensive sequence conservation, our findings support the notion that the combination of short transcription factor binding site motifs are able to convey enhancer function 50 and mediate the regulatory activity across evolutionary time.…”

Section: Lamprey Soxe1 Enhancer Activity Is Conserved In Gnathostomessupporting

confidence: 75%

A genome-wide assessment of the ancestral neural crest gene regulatory network

Hockman

Chong

Gavriouchkina

et al. 2018

Preprint

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The neural crest is an embryonic cell population that contributes to key vertebrate-specific features including the craniofacial skeleton and peripheral nervous system. Here we examine the transcriptional profiles and chromatin accessibility of neural crest cells in the basal sea lamprey, in order to gain insight into the ancestral state of the neural crest gene regulatory network (GRN) at the dawn of vertebrates. Transcriptome analyses reveal clusters of co-regulated genes during neural crest specification and migration that show high conservation across vertebrates for dynamic programmes like Wnt modulation during the epithelial to mesenchymal transition, but also reveal novel transcription factors and cell-adhesion molecules not previously implicated in neural crest migration. ATAC-seq analysis refines the location of known cis-regulatory elements at the Hox-α2 locus and uncovers novel cis-regulatory elements for Tfap2B and SoxE1. Moreover, cross-species deployment of lamprey elements in zebrafish reveals that the lamprey SoxE1 enhancer activity is deeply conserved, mediating homologous expression in jawed vertebrates. Together, our data provide new insight into the core elements of the GRN that are conserved to the base of the vertebrates, as well as expose elements that are unique to lampreys.

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Section: Lamprey Soxe1 Enhancer Activity Is Conserved In Gnathostomessupporting

confidence: 75%

A genome-wide assessment of the ancestral neural crest gene regulatory network

Hockman

Chong

Gavriouchkina

et al. 2018

Preprint

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“…Similarly, in insects, some enhancers of "even-skipped" (24) and of some dorso-ventral patterning genes (25) have maintained their ancestral positions. Within single svb enhancers, DNA sequences have diverged substantially without causing major changes in enhancer function, a feature that has been observed previously (26). However, at a larger scale, the functional organization of the whole svb regulatory region has been largely conserved.…”

Section: Discussionmentioning

confidence: 59%

Conserved regulatory architecture underlies parallel genetic changes and convergent phenotypic evolution

Frankel

Wang

Stern

2012

Proc. Natl. Acad. Sci. U.S.A.

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Similar morphological, physiological, and behavioral features have evolved independently in different species, a pattern known as convergence. It is known that morphological convergence can occur through changes in orthologous genes. In some cases of convergence, cis-regulatory changes generate parallel modifications in the expression patterns of orthologous genes. Our understanding of how changes in cis-regulatory regions contribute to convergence is hampered, usually, by a limited understanding of the global cis-regulatory structure of the evolving genes. Here we examine the genetic causes of a case of precise phenotypic convergence between Drosophila sechellia and Drosophila ezoana, species that diverged ∼40 Mya. Previous studies revealed that changes in multiple transcriptional enhancers of shavenbaby (svb, a transcript of the ovo locus) caused phenotypic evolution in the D. sechellia lineage. It has also been shown that the convergent phenotype of D. ezoana was likely caused by cis-regulatory evolution of svb. Here we show that the large-scale cis-regulatory architecture of svb is conserved between these Drosophila species. Furthermore, we show that the D. ezoana orthologs of the evolved D. sechellia enhancers have also evolved expression patterns that correlate precisely with the changes in the phenotype. Our results suggest that phenotypic convergence resulted from multiple noncoding changes that occurred in parallel in the D. sechellia and D. ezoana lineages.parallel developmental evolution | evolutionary developmental biology | enhancer function

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“…Actually, none of the tested methods for scoring conservation could improve the sensitivity significantly. This may seem surprising, since it is well established that conservation information helps to uncover functional genomic elements (Meireles-Filho and Stark 2009;Lindblad-Toh et al 2011). However, these successful studies looked at the most conserved genomic elements, which are probably almost always functional.…”

Section: Negligible Improvement Through Sequence Conservationmentioning

confidence: 99%

P-value-based regulatory motif discovery using positional weight matrices

et al. 2012

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To analyze gene regulatory networks, the sequence-dependent DNA/RNA binding affinities of proteins and noncoding RNAs are crucial. Often, these are deduced from sets of sequences enriched in factor binding sites. Two classes of computational approaches exist. The first describe binding motifs by sequence patterns and search the patterns with highest statistical significance for enrichment. The second class uses the more powerful position weight matrices (PWMs). Instead of maximizing the statistical significance of enrichment, they maximize a likelihood. Here we present XXmotif (eXhaustive evaluation of matriX motifs), the first PWM-based motif discovery method that can optimize PWMs by directly minimizing their P-values of enrichment. Optimization requires computing millions of enrichment P-values for thousands of PWMs. For a given PWM, the enrichment P-value is calculated efficiently from the match P-values of all possible motif placements in the input sequences using order statistics. The approach can naturally combine P-values for motif enrichment, conservation, and localization. On ChIP-chip/seq, miRNA knock-down, and coexpression data sets from yeast and metazoans, XXmotif outperformed state-of-the-art tools, both in numbers of correctly identified motifs and in the quality of PWMs. In segmentation modules of D. melanogaster, we detect the known key regulators and several new motifs. In human core promoters, XXmotif reports most previously described and eight novel motifs sharply peaked around the transcription start site, among them an Initiator motif similar to the fly and yeast versions. XXmotif's sensitivity, reliability, and usability will help to leverage the quickly accumulating wealth of functional genomics data.[Supplemental material is available for this article.]The rapid progress in high-throughput sequencing is transforming the way in which we study genomes and their role in regulating cellular and developmental processes. Increasingly, single-locus and single-gene approaches are replaced by genome-wide measurements. Whether it be ChIP-seq (Johnson et al. 2006 (Lieberman-Aiden et al. 2009), most of these experiments need to be analyzed with respect to protein and noncoding RNA (ncRNA) factors that bind to specific sequences in the genome or transcriptome. These binding events are the key to understanding regulatory processes because, unlike epigenetic marks, only the genomic sequence carries information at a density that is sufficient to target factors unambiguously to specific loci or transcripts.Therefore, finding binding motifs for regulatory factors that are expected to be enriched in certain sequences is of central importance in the analysis of most of these types of experiments. This has led to a growing interest in tools for de novo motif finding (Tompa et al. 2005;Sandve et al. 2007). De novo motif discovery methods search for motifs of binding sites that are enriched in a positive sequence set in comparison to a negative sequence set or to a statistical background model derived from su...

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Comparative genomics of gene regulation—conservation and divergence of cis-regulatory information

Cited by 78 publications

References 71 publications

A genome-wide assessment of the ancestral neural crest gene regulatory network

A genome-wide assessment of the ancestral neural crest gene regulatory network

Conserved regulatory architecture underlies parallel genetic changes and convergent phenotypic evolution

P-value-based regulatory motif discovery using positional weight matrices

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