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Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci (4C-seq)

ABSTRACT: Hox genes are required during the morphogenesis of both vertebrate digits and external genitals.We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal.We propose that this convergent regulatory evolution was triggered by the pre-existence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates.

ORGANISM(S): Mus musculus

PROVIDER: GSE62265 | GEO | 2014/11/21

SECONDARY ACCESSION(S): PRJNA263615

REPOSITORIES: GEO

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Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci (RNA-seq)

Project description:Hox genes are required during the morphogenesis of both vertebrate digits and external genitals.We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal.We propose that this convergent regulatory evolution was triggered by the pre-existence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates. RNA-seq from mouse E12.5 digits cells and mouse E15.5 genital tubercle cells.

2014-11-21 | E-GEOD-62268 | biostudies-arrayexpress

Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci (4C-seq)

Project description:Hox genes are required during the morphogenesis of both vertebrate digits and external genitals.We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal.We propose that this convergent regulatory evolution was triggered by the pre-existence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates. Circular Chromosome Conformation Capture (4C-seq) samples from mouse digit cells and mouse genital tubercle cells performed as previously described (Noordermeer et al. 2011)

2014-11-21 | E-GEOD-62265 | biostudies-arrayexpress

Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci (tiling)

Project description:Hox genes are required during the morphogenesis of both vertebrate digits and external genitals.We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal.We propose that this convergent regulatory evolution was triggered by the pre-existence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates. Chromatin ImmoPrecipitation on chip (Tiling array): Distribution of H3K27ac and H3K27me3 in WT genital tubercle (GT) at E13.5 and E15.5 Distribution of H3K27ac WT forelimb autopods are from Montavon et al., 2011.

2014-11-21 | E-GEOD-62073 | biostudies-arrayexpress

Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci (tiling)

2014-11-21 | GSE62073 | GEO

Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci (RNA-seq)

2014-11-21 | GSE62268 | GEO

Transcription landscape at the HoxD locus in developing limbs and brain

Project description:The emergence and evolution of digits was an essential step in the success of the tetrapod lineage. Amongst the key players, Hoxd genes were functionally co-opted in the developing digital plate, where they help organize growth and patterns. To understand both the evolutionary recruitment and transcriptional regulation of this genomic locus, we analyzed its architecture and chromatin status in developing digits, combined with a deletion approach in vivo. We show that the active and inactive parts of the gene cluster adopt opposite spatial configurations, corresponding to different chromatin domains. Active genes are contacted by several regulatory islands, located within a neighboring gene desert, which contribute quantitatively or qualitatively to the global transcriptional readout. We refer to this novel type of control as a ‘regulatory archipelago’ and discuss the value of this concept to understand both the morphological flexibility of tetrapod digits and the robustness of the underlying developmental process. Transcriptional activity at the Hoxd locus in developing limbs and brain at E12.5

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Conservation and divergence of regulatory strategies and the origin of tetrapod digits

Project description:The evolution of tetrapod limbs from fish fins enabled the conquest of land by vertebrates and thus represents a key step in evolution. Despite the use of comparative gene expression analyses, critical aspects of this transformation remain controversial, in particularly the origin of digits. Hoxa and Hoxd genes are essential for the specification of the different limb segments and their functional abrogation leads to large truncations of the appendages. Here we show that the selective transcription of mouse Hoxa genes in proximal and distal limbs is related to a bimodal higher order chromatin structure, similar to that reported for Hoxd genes, thus revealing a generic regulatory strategy implemented by both gene clusters during limb development. We found the same bimodal chromatin architecture in fish embryos, indicating that the regulatory strategy used to pattern tetrapod limbs predates the divergence between fish and tetrapods. However, when assessed in mice, both fish regulatory domains triggered transcription in proximal, rather than distal limb territories, supporting an evolutionary scenario whereby digits arose as true tetrapod novelties through genetic retrofitting of a preexisting bimodal chromatin framework. We discuss the possibility to consider regulatory circuitries, rather than expression patterns, as essential parameters to define evolutionary synapomorphies. Circular Chromosome Conformation Capture (4C seq) at the mouse HoxA and HoxD loci in proximal and distal forelimbs and forebrain at E12.5 and at the zebrafish HoxAa, HoxAb and HoxDa loci in 5 dpf whole embryos.

2014-01-21 | E-GEOD-47644 | biostudies-arrayexpress

Conservation and divergence of regulatory strategies and the origin of tetrapod digits

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Spatial organization of chromatin at the HoxD locus in developing limbs and brain

Project description:The emergence and evolution of digits was an essential step in the success of the tetrapod lineage. Amongst the key players, Hoxd genes were functionally co-opted in the developing digital plate, where they help organize growth and patterns. To understand both the evolutionary recruitment and transcriptional regulation of this genomic locus, we analyzed its architecture and chromatin status in developing digits, combined with a deletion approach in vivo. We show that the active and inactive parts of the gene cluster adopt opposite spatial configurations, corresponding to different chromatin domains. Active genes are contacted by several regulatory islands, located within a neighboring gene desert, which contribute quantitatively or qualitatively to the global transcriptional readout. We refer to this novel type of control as a ‘regulatory archipelago’ and discuss the value of this concept to understand both the morphological flexibility of tetrapod digits and the robustness of the underlying developmental process. Chromosome Conformation Capture-on-chip analysis (4C) at the Hoxd locus in developing limbs and brain at E12.5

2011-11-28 | GSE31658 | GEO

Chromatin landscape at the HoxD locus in developing digits and forebrain

Project description:The emergence and evolution of digits was an essential step in the success of the tetrapod lineage. Amongst the key players, Hoxd genes were functionally co-opted in the developing digital plate, where they help organize growth and patterns. To understand both the evolutionary recruitment and transcriptional regulation of this genomic locus, we analyzed its architecture and chromatin status in developing digits, combined with a deletion approach in vivo. We show that the active and inactive parts of the gene cluster adopt opposite spatial configurations, corresponding to different chromatin domains. Active genes are contacted by several regulatory islands, located within a neighboring gene desert, which contribute quantitatively or qualitatively to the global transcriptional readout. We refer to this novel type of control as a ‘regulatory archipelago’ and discuss the value of this concept to understand both the morphological flexibility of tetrapod digits and the robustness of the underlying developmental process. Distribution of histone marks and RNA Pol2 at the Hoxd locus in developing limbs and brain at E12.5

2011-11-28 | GSE31654 | GEO

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