Deep conservation of<i>cis</i>-regulatory elements in metazoans

Maeso, Ignacio; Irimia, Manuel; Tena, Juan J.; Casares, Fernando; Gómez-Skármeta, José Luis

doi:10.1098/rstb.2013.0020

Cited by 28 publications

(22 citation statements)

References 122 publications

(189 reference statements)

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“…they contain the same collection of TF recognition motifs, although located at different positions within the DHS) and in many cases, they also maintain the same tissue specific activities [6]. Similar to this latter case, two studies comparing orthologous regulatory landscapes in different insect species have shown that functionally equivalent enhancers are maintained at equivalent genomic positions, even though their underlying sequences have diverged beyond recognition [83,84], as it has been discussed elsewhere [15,85].…”

Section: Permissive Genomic Environments For Enhancer Evolution At Thmentioning

confidence: 76%

“…Furthermore, the distribution of functional elements in the genome, and of CREs in particular, is far from being uniform. Highly distinctive features demarcate the genes and genomic regions around developmental genes, with much larger intergenic distances, longer and more numerous introns and higher evolutionary constraint, both in terms of sequence and synteny conservation [11][12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework

Maeso

Tena

2016

Seminars in Cell & Developmental Biology

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Cis-regulatory changes are arguably the primary evolutionary source of animal morphological diversity. With the recent explosion of genome-wide comparisons of the cis-regulatory content in different animal species is now possible to infer general principles underlying enhancer evolution. However, these studies have also revealed numerous discrepancies and paradoxes, suggesting that the mechanistic causes and modes of cis-regulatory evolution are still not well understood and are probably much more complex than generally appreciated. Here, we argue that the mutational mechanisms and genomic regions generating new regulatory activities must comply with the constraints imposed by the molecular properties of cis-regulatory elements (CREs) and the organizational features of long-range chromatin interactions. Accordingly, we propose a new integrative evolutionary framework for cis-regulatory evolution based on two major premises for the origin of novel enhancer activity: (i) an accessible chromatin environment and (ii) compatibility with the 3D structure and interactions of pre-existing CREs. Mechanisms and DNA sequences not fulfilling these premises, will be less likely to have a measurable impact on gene expression and as such, will have a minor contribution to the evolution of gene regulation. Finally, we discuss current comparative cis-regulatory data under the light of this new evolutionary model, and propose that the two most prominent mechanisms for the evolution of cis-regulatory changes are the overprinting of ancestral CREs and the exaptation of transposable elements.

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Section: Permissive Genomic Environments For Enhancer Evolution At Thmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework

Maeso

Tena

2016

Seminars in Cell & Developmental Biology

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“…Deep regulatory homologies, at distances where genomes have diverged too far to make use of sequence alignment—even trans-phyletically—have been reported previously [47, 52], but the challenges inherent in identifying homologous CRMs have kept examples to a minimum (see Outstanding Questions). Furthermore, conservation of function does not always mean conservation of mechanism.…”

Section: Concluding Remarks: An Exciting Time For Studies Of Grn Evolmentioning

confidence: 99%

Perspectives on Gene Regulatory Network Evolution

Halfon

2017

Trends in Genetics

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Animal development proceeds through the activity of genes and their cis-regulatory modules, working together in sets of gene regulatory networks (GRNs). Emergence of species-specific traits and novel structures results from evolutionary changes in GRNs. Recent work in a wide variety of animal models, and particularly in insects, has started to reveal the modes and mechanisms of GRN evolution. I discuss here different aspects of GRN evolution and argue that developmental system drift, in which conserved phenotype is nevertheless a result of changed genetic interactions, should regularly be viewed from the perspective of GRN evolution. Advances in methods to discover related cis-regulatory modules in diverse insect species, a critical requirement for detailed GRN characterization, are also described.

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“…Latest evidences are highlighting that divergence in cis -regulatory sequences might underlie phenotypic diversity in evolution more commonly than divergence in the sequences of the TFs themselves. Gain, loss or changes in the affinity of TFs at the level of REs can indeed shape gene regulatory networks [ 1 ] [ 2 ]. In addition, co-evolution of cis -regulatory elements and of TF proteins is emerging as an extremely important evolutionary process, defined as cis-trans co-evolution [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Evolution of p53 Transactivation Specificity through the Lens of a Yeast-Based Functional Assay

et al. 2015

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Co-evolution of transcription factors (TFs) with their respective cis-regulatory network enhances functional diversity in the course of evolution. We present a new approach to investigate transactivation capacity of sequence-specific TFs in evolutionary studies. Saccharomyces cerevisiae was used as an in vivo test tube and p53 proteins derived from human and five commonly used animal models were chosen as proof of concept. p53 is a highly conserved master regulator of environmental stress responses. Previous reports indicated conserved p53 DNA binding specificity in vitro, even for evolutionary distant species. We used isogenic yeast strains where p53-dependent transactivation was measured towards chromosomally integrated p53 response elements (REs). Ten REs were chosen to sample a wide range of DNA binding affinity and transactivation capacity for human p53 and proteins were expressed at two levels using an inducible expression system. We showed that the assay is amenable to study thermo-sensitivity of frog p53, and that chimeric constructs containing an ectopic transactivation domain could be rapidly developed to enhance the activity of proteins, such as fruit fly p53, that are poorly effective in engaging the yeast transcriptional machinery. Changes in the profile of relative transactivation towards the ten REs were measured for each p53 protein and compared to the profile obtained with human p53. These results, which are largely independent from relative p53 protein levels, revealed widespread evolutionary divergence of p53 transactivation specificity, even between human and mouse p53. Fruit fly and human p53 exhibited the largest discrimination among REs while zebrafish p53 was the least selective.

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Deep conservation ofcis-regulatory elements in metazoans

Cited by 28 publications

References 122 publications

Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework

Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework

Perspectives on Gene Regulatory Network Evolution

Evolution of p53 Transactivation Specificity through the Lens of a Yeast-Based Functional Assay

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