Conserved noncoding elements and the evolution of animal body plans

Vavouri, Tanya; Lehner, Ben

doi:10.1002/bies.200900014

Cited by 28 publications

(23 citation statements)

References 67 publications

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“…This assumption is supported by the known association of conserved non-coding sequences with developmentally important genes, as well as the identification of conserved non-coding sequences that can drive gene expression during development (reviewed by Elgar, 2009;Vavouri and Lehner, 2009). However, recent studies (discussed below) have provided evidence that conserved cisregulatory sequences do not always have conserved function, and functionally conserved CRMs do not always have conserved sequence.…”

Section: Introductionmentioning

confidence: 99%

Conserved non-coding elements and cis regulation: actions speak louder than words

Nelson

Wardle

2013

Development

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It is a truth (almost) universally acknowledged that conserved non-coding genomic sequences function in the cis regulation of neighbouring genes. But is this a misconception? The literature is strewn with examples of conserved non-coding sequences being able to drive reporter expression, but the extent to which such sequences are actually used endogenously in vivo is only now being rigorously explored using unbiased genome-scale approaches. Here, we review the emerging picture, examining the extent to which conserved non-coding sequences equivalently regulate gene expression in different species, or at different developmental stages, and how genomics approaches are revealing the relationship between sequence conservation and functional use of cis-regulatory elements.

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Section: Introductionmentioning

confidence: 99%

Conserved non-coding elements and cis regulation: actions speak louder than words

Nelson

Wardle

2013

Development

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“…Other studies use DNA sequence signatures, mainly evolutionary conservation and/or clustering of predicted TF binding motifs, to screen genomes for enhancers [16][17][18][19]. These methods have also been successful, although again, they are by no means foolproof: for example, not all functional enhancers show evidence of evolutionary sequence conservation-even if their function is conserved-and conversely, not all highly conserved sequences display regulatory activity [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Low-affinity transcription factor binding sites shape morphogen responses and enhancer evolution

Ramos

Barolo

2013

Phil. Trans. R. Soc. B

109

113

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In the era of functional genomics, the role of transcription factor (TF)–DNA binding affinity is of increasing interest: for example, it has recently been proposed that low-affinity genomic binding events, though frequent, are functionally irrelevant. Here, we investigate the role of binding site affinity in the transcriptional interpretation of Hedgehog (Hh) morphogen gradients . We noted that enhancers of several Hh-responsive Drosophila genes have low predicted affinity for Ci, the Gli family TF that transduces Hh signalling in the fly. Contrary to our initial hypothesis, improving the affinity of Ci/Gli sites in enhancers of dpp , wingless and stripe , by transplanting optimal sites from the patched gene, did not result in ectopic responses to Hh signalling. Instead, we found that these enhancers require low-affinity binding sites for normal activation in regions of relatively low signalling. When Ci/Gli sites in these enhancers were altered to improve their binding affinity, we observed patterning defects in the transcriptional response that are consistent with a switch from Ci-mediated activation to Ci-mediated repression. Synthetic transgenic reporters containing isolated Ci/Gli sites confirmed this finding in imaginal discs. We propose that the requirement for gene activation by Ci in the regions of low-to-moderate Hh signalling results in evolutionary pressure favouring weak binding sites in enhancers of certain Hh target genes.

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“…Notably, a large proportion of them are highly conserved in the genomes of many animal groups. These Conserved Non-coding Elements (CNEs) represent a set of transcriptional enhancers that regulate the expression of genes coding for proteins involved in developmental pathways (Vavouri and Lehner 2009). …”

Section: Non-coding Regulatory Elementsmentioning

confidence: 99%

Breaking Mariano Artigas’ Frontiers of Evolutionism

Novo

2016

SetF

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Abstract. I review Mariano Artigas' appraisal of Evolution as reflected in some of his works. I find that his perception of evolutionary theory changed from a critical attitude, mainly directed against the modern synthesis of the twentieth century, to a more lenient approach as he incorporated new elements into his reflections. However, he did not fully appreciate some of the advances made in evolutionary biology in recent years. I provide some examples, taken from the field of evolutionary genomics, which shed new light on why evolvability is a necessary property of living beings and how adaptation proceeds through the rewiring of modular gene regulatory networks, resulting in a remarkable degree of phenotypic plasticity. This view provides a richer understanding of two key elements of Artigas' portrayal of the modern worldview: dynamism and patterning.

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Conserved noncoding elements and the evolution of animal body plans

Cited by 28 publications

References 67 publications

Conserved non-coding elements and cis regulation: actions speak louder than words

Conserved non-coding elements and cis regulation: actions speak louder than words

Low-affinity transcription factor binding sites shape morphogen responses and enhancer evolution

Breaking Mariano Artigas’ Frontiers of Evolutionism

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