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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. Circular Chromosome Conformation Capture (4C-seq) samples from mouse digit cells and mouse genital tubercle cells performed as previously described (Noordermeer et al. 2011)

ORGANISM(S): Mus musculus

SUBMITTER: Nicolas Lonfat

PROVIDER: E-GEOD-62265 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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 (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.

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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)

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

2014-11-21 | GSE62265 | GEO

Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-11-21 | E-GEOD-62269 | biostudies-arrayexpress

4C-seq: Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci

Project description:Hox genes are essential regulators of embryonic development. They are activated in a temporal sequence following their topological order within their genomic clusters. Subsequently, states of activity are fine-tuned and maintained to translate into domains of progressively overlapping gene products. While the mechanisms underlying such temporal and spatial progressions begin to be understood, many of their aspects remain unclear. We have systematically analyzed the 3D chromatin organization of Hox clusters in vivo, during their activation using high-resolution circular chromosome conformation capture (4C-seq). Initially, Hox clusters are organized as single 3D chromatin compartments decorated with bivalent chromatin marks. Their progressive transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch one after the other, from an inactive to an active 3D compartment. These local 3D dynamics occur within a larger constitutive framework of interactions within the surrounding Topological Associated Domains, which confirms previous results that regulation of this process in primarily cluster intrinsic. The local step-wise progression in time can be stopped and memorized at various body levels and hence it may accounts for the various chromatin architectures previously described at different anterior to posterior body levels for the same embryo at a later stage. Circular Chromosome Conformation Capture (4C-seq) samples from mouse ES cells and mouse embryonic samples at different stages of development. Data based on 41 biological samples.

2014-04-28 | E-GEOD-55342 | biostudies-arrayexpress

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

Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci

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2014-04-28 | E-GEOD-55344 | biostudies-arrayexpress

Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution

Project description:Phenotypic differences between closely related species are thought to arise primarily from changes in gene expression due to mutations in cis-regulatory sequences (enhancers). However, it has remained unclear, how frequently mutations alter enhancer activity or create functional enhancers de novo. Here, we use STARR-seq, a recently developed quantitative enhancer assay, to determine genome-wide enhancer activity profiles for five Drosophila species in the constant trans-regulatory environment of D. melanogaster S2 cells. We find that the function of a large fraction of D. melanogaster enhancers is conserved in their orthologous sequences due to selection and stabilizing turnover of transcription factor motifs. Moreover, hundreds of enhancers have been gained since the D. melanogaster M-bM-^@M-^S D. yakuba split about 11 million years ago without apparent adaptive selection and can contribute to gene expression changes in vivo. Our finding that enhancer activity is often deeply conserved and frequently gained provides important functional insights into regulatory evolution. STARR-seq was performed in S2 cells with paired-end sequencing in two replicates and respective inputs using genomic DNA from different Drosophila species. RNA-seq was performed in a non-stranded manner without replicates for two Drosophila species.

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