Reshuffling genomic landscapes to study the regulatory evolution of
            <i>Hox</i>
            gene clusters

Tschopp, Patrick; Fraudeau, N.; Béna, Frédérique; Duboule, Denis

doi:10.1073/pnas.1102985108

Cited by 12 publications

(10 citation statements)

References 41 publications

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“…The genes involved are exemplar developmental genes present at the HOXA (human HOXA1-A7; Figure 2B) and HOXD (human HOXD1-4) clusters. Both clusters are implicated in multiple cancers and other disorders, and are tightly regulated via higher order chromatin domains [38], [39]. It is thought that structural divergence within the chromatin domains harbouring these clusters underlies many important innovations in the vertebrate body plan [40].…”

Section: Resultsmentioning

confidence: 99%

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

2013

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Several recent studies have examined different aspects of mammalian higher order chromatin structure – replication timing, lamina association and Hi-C inter-locus interactions — and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin structure has played important roles during evolution.

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Section: Resultsmentioning

confidence: 99%

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

2013

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“…B) (Zákány et al, ; Spitz et al, ; Andrey et al, ). As in the spinal cord and somites, the proximity to the long‐range cis‐acting elements rather than promoter specificity defines the levels of Hox gene activation in developing limbs (Tarchini and Duboule, ; Montavon et al, ; Tschopp et al, ). The chromosome conformation capture on chip (4C) technique (Splinter et al, ) revealed that the transcriptionally active Hoxd11‐9 genes interact predominantly with the telomeric gene desert in proximal limbs (Fig.…”

Section: Cis‐regulatory Elementsmentioning

confidence: 99%

Hox genes regulation in vertebrates

Soshnikova

2013

Developmental Dynamics

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Hox genes encode transcription factors defining cellular identities along the major and secondary body axes. Their coordinated expression in both space and time is critical for embryonic patterning. Accordingly, Hox genes transcription is tightly controlled at multiple levels, and involves an intricate combination of local and long-range cis-regulatory elements. Recent studies revealed that in addition to transcription factors, dynamic patterns of histone marks and higher-order chromatin structure are important determinants of Hox gene regulation. Furthermore, the emerging picture suggests an involvement of various species of non-coding RNA in targeting activating and repressive complexes to Hox clusters. I review these recent developments and discuss their relevance to the control of Hox gene expression in vivo, as well as to our understanding of transcriptional regulatory mechanisms. Developmental Dynamics 243:49-58,

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“…In one example, using a novel approach in which a targeted translocation was induced in the mouse genome, 104 Duboule's group placed the HoxC gene cluster under the regulatory control of the HoxD genomic locus and tested its ability to rescue HoxD loss-of-function phenotypes, which include defects in digit formation. 105 Their studies showed the HoxC cluster was largely able to rescue HoxD mutants, providing a compelling example of the importance of regulatory evolution within Hox complexes. Thus, after the duplication of Hox complexes in vertebrates, redundancy permitted diversification of highly related paralogs.…”

Section: Cis-regulatory Changes In Vertebrate Hox Complexesmentioning

confidence: 99%

Hoxgene evolution: multiple mechanisms contributing to evolutionary novelties

Pick¹,

Heffer²

2012

Annals of the New York Academy of Sciences

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Hox genes, which are important for determining regional identity in organisms as diverse as flies and humans, are typically considered to be under strong evolutionary constraints because large changes in body plan are usually detrimental to survival. Despite this, there is great body plan diversity in nature, and many of the mechanisms underlying this diversity have been attributed to changes in Hox genes. Over the past year, several studies have examined how Hox genes play a role in evolution of body plans and novelties. Here, we examine four distinct evolutionary mechanisms implicated in Hox gene evolution, which include changes in (1) Hox gene expression, (2) downstream Hox target gene regulation without change in Hox expression, (3) protein-coding sequence, and (4) posttranscriptional regulation of Hox gene function. We discuss how these types of changes in Hox genes--once thought to be evolutionarily static--underlie morphological diversification. We review recent studies that highlight each of these mechanisms and discuss their roles in the evolution of morphology and novelties.

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Reshuffling genomic landscapes to study the regulatory evolution of Hox gene clusters

Cited by 12 publications

References 41 publications

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

Hox genes regulation in vertebrates

Hoxgene evolution: multiple mechanisms contributing to evolutionary novelties

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