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The Dynamic Architecture of Hox Gene Clusters

ABSTRACT: The spatial and temporal control of Hox gene transcription is essential for patterning the vertebrate body axis. Although this process involves changes in histone posttranslational modifications, the existence of particular three-dimensional (3D) architectures remained to be assessed in vivo. Using high-resolution chromatin conformation capture methodology, we examined the spatial configuration of Hox clusters in embryonic mouse tissues where different Hox genes are active. When the cluster is transcriptionally inactive, Hox genes associate into a single 3D structure delimited from flanking regions. Once transcription starts, Hox clusters switch to a bimodal 3D organization where newly activated genes progressively cluster into a transcriptionally active compartment. This transition in spatial configurations coincides with the dynamics of chromatin marks, which label the progression of the gene clusters from a negative to a positive transcription status. This spatial compartmentalization may be key to process the collinear activation of these compact gene clusters.

ORGANISM(S): Mus musculus

PROVIDER: GSE31570 | GEO | 2011/10/13

SECONDARY ACCESSION(S): PRJNA145705

REPOSITORIES: GEO

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The Dynamic Architecture of Hox Gene Clusters

Project description:The spatial and temporal control of Hox gene transcription is essential for patterning the vertebrate body axis. Although this process involves changes in histone posttranslational modifications, the existence of particular three-dimensional (3D) architectures remained to be assessed in vivo. Using high-resolution chromatin conformation capture methodology, we examined the spatial configuration of Hox clusters in embryonic mouse tissues where different Hox genes are active. When the cluster is transcriptionally inactive, Hox genes associate into a single 3D structure delimited from flanking regions. Once transcription starts, Hox clusters switch to a bimodal 3D organization where newly activated genes progressively cluster into a transcriptionally active compartment. This transition in spatial configurations coincides with the dynamics of chromatin marks, which label the progression of the gene clusters from a negative to a positive transcription status. This spatial compartmentalization may be key to process the collinear activation of these compact gene clusters. Examination of gene expression in 3 cell types. Examination of 2 different histone modifications in 2 cell types.

2011-10-12 | E-GEOD-31570 | biostudies-arrayexpress

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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

RNA-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. RNA-seq from mouse ES cells and mouse embryonic stage E10.5 forebrain. Data based on 2 biological samples.

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ChIP-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. ChIP-seq samples (H3K4me3 and H3K27me3) from mouse ES cells and mouse embryonic stage E8.5 pre-somitic mesoderm. Data based on 4 biological samples.

2014-04-28 | E-GEOD-54955 | biostudies-arrayexpress

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A single 3D chromatin compartment in amphioxus Hox cluster suggests a stepwise evolutionary origin for vertebrate Hox bimodal regulatory topologies

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Construction of Danio rerio Asymmetrical Maps (DreAM)

Project description:Purpose: Construction of 3D zebrafish spatial transcriptomics data for studying the establishment of AP axis. Methods: We performed serial bulk RNA-seq data of zebrafish embryo at three development points. Using the published spatial transcriptomics data as references, we implemented Palette to infer spatial gene expression from bulk RNA-seq data and constructed 3D embryonic spatial transcriptomics. The constructed 3D transcriptomics data was then projected on zebrafish embryo images with 3D coordinates, establishing a spatial gene expression atlas named Danio rerio Asymmetrical Maps (DreAM). Results: DreAM provides a powerful platform for visualizing gene expression patterns on zebrafish morphology and investigating spatial cell-cell interactions. Conclusions: Our work used DreAM to explore the establishment of anteroposterior (AP) axis, and identified multiple morphogen gradients that played essential roles in determining cell AP positions. Finally, we difined a hox score, and comprehensively demonstrated the spatial collinearity of Hox genes at single-cell resolution during development.

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A Switch Between Topological Domains Underlies HoxD Genes Collinearity in Mouse Limbs (4C-Seq)

Project description:During limb development, Hoxd genes are transcribed in two waves: Early on, when the arm and forearm are specified and subsequently, when digits form. While the latter phase is controlled by enhancers centromeric to the HoxD cluster, we show here that the early phase requires enhancers located in the opposite telomeric gene desert. The transition between the two types of regulations involves a functional switch between two distinct topological domains, as reflected by a subset of genes mapping centrally into the cluster, which initially interact with the telomeric domain and subsequently shift to establish new contacts on the opposite side. This transition between two regulatory landscapes generates an intermediate area of low Hox dose developing into the wrist, the transition between our arms and our hands. This intriguing correspondence between genomic and morphological boundaries illustrates the mechanism underlying collinear Hox gene regulation in our developing appendages. Circular Chromosome Conformation Capture (4C seq) at the HoxD locus in developing proximal and distal limbs at E9.5 and E12.5

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