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

ABSTRACT: Comparison among vertebrates and the cephalochordate amphioxus Hox clusters architectures 4C-seq experiments from promoters spanning the amphioxus Hox cluster and the zebrafish hoxd cluster and surrounnding areas,

ORGANISM(S): Branchiostoma lanceolatum

SUBMITTER: Juan Tena

PROVIDER: E-GEOD-68737 | biostudies-arrayexpress |

REPOSITORIES: 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

Project description:Comparison among vertebrates and the cephalochordate amphioxus Hox clusters architectures

2015-12-16 | GSE68737 | GEO

Chromatin structure dynamics of hoxa13a, hoxa13b and hoxd13a loci during zebrafish development.

Project description:We designed 4C-Seq experiments for hoxa13a, hoxa13b and hoxd13a promoters in three developmental stages in zebrafish embryos: 24, 48 and 60 hpf. 4C-seq samples for three different hox13 genes promoters in three developmental stages in zebrafish embryos: 24, 48 and 60 hpf.

2015-01-06 | E-GEOD-61063 | biostudies-arrayexpress

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

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

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Obesity-associated variants within FTO form long-range functional connections with IRX3

Project description:Genome-wide association studies in diverse populations have reproducibly associated variants within introns of FTO with increased risk for obesity and type-2 diabetes.While the molecular mechanisms linking these noncoding variants with obesity are not immediately obvious, subsequent studies in mice demonstrated that FTO expression levels influence body mass and composition phenotypes. Yet, no direct connection between the obesity-associated intronic variants and FTO expression or function has been made. We show that the obesity-associated noncoding sequences within FTO are functionally connected, at megabase distances, primarily with the homeobox gene IRX3, rather than with FTO. 4C-seq samples for Fto/fto and Irx3/irx3a genes promoters in different samples: adult mouse brain, E9.5 mouse embryos and 24hpf zebrafish embryos.

2014-02-24 | E-GEOD-52830 | biostudies-arrayexpress

Evolutionary comparison reveals that diverging CCCTC-binding factor (CTCF) sites are signatures of ancestral topological associating domains borders

Project description:Comparison of conserved TAD boundaries reveals that diverging CTCF sites is an evolutionary conserved signature associated with TAD borders 4C-seq samples for six gene family promoters in different samples: E9.5 and E14.5 mouse embryos ; 24hpf, 48hpf, 80%epiboly and Dome zebrafish embryos ; 48hpf S.purpuratus embryos

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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.

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The Dynamic Architecture of Hox Gene Clusters

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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.

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Synthetic genomic reconstitution reveals principles of mammalian Hox cluster regulation [DNA-Seq]

Project description:Precise Hox gene expression is crucial for embryonic patterning. Local transcription factor binding and distal enhancer elements have emerged as the major regulatory modes controlling the initiation and maintenance of Hox gene expression. However, quantifying their relative contributions has remained elusive. Here, we introduce ‘synthetic regulatory reconstitution’, a novel conceptual framework for studying gene regulation and apply it to the mammalian HoxA cluster. To measure the HoxA intrinsic regulatory potential and distal enhancer contributions, we de novo synthesized and delivered variant rat HoxA clusters (130-170 kilobases each) to an ectopic location in the mouse genome. We find that a minimal HoxA cluster lacking distal enhancers induces the appropriate gene set and establishes distinct chromatin domains in response to patterning signals, while distal enhancers are required for full transcriptional output. These results suggest that the genomically compact Hox clusters contain all the information to decode patterning signals and maintain positional information

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