Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE55344 | GEO | 2014/04/28
SECONDARY ACCESSION(S): PRJNA239362
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-04-28 | E-GEOD-55344 | biostudies-arrayexpress
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
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.
2014-04-28 | E-GEOD-54952 | biostudies-arrayexpress
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
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.
2014-04-28 | GSE55342 | GEO
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.
2014-04-28 | GSE54952 | GEO
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.
2014-04-28 | GSE54955 | GEO
Project description:We present a strategy to examine the chromatin conformation of individual loci in specific cell types during Drosophila embryogenesis. Regulatory DNA is tagged with binding sites (lacO) for LacI, which is used to immunoprecipitate the tagged chromatin from specific cell types. We applied this approach to Distalless (Dll), a gene required for limb development in Drosophila. We show that the local chromatin conformation at Dll depends on the cell type: in cells that express Dll, the 5' regulatory region is in close proximity to the Dll promoter. In Dll-nonexpressing cells this DNA is in a more extended configuration. In addition, transcriptional activators and repressors are bound to Dll regulatory DNA in a cell type-specific manner. The pattern of binding by GAGA factor and the variant histone H2Av suggest that they play a role in the regulation of Dll chromatin conformation in expressing and nonexpressing cell types, respectively.
| S-EPMC3329935 | biostudies-literature
Project description:Recent studies have demonstrated that chromatin architecture is linked to the progression of cancers. However, the roles of 3D structure and its dynamics in hormone-dependent breast cancer and endocrine resistance are largely unknown. Here we report the dynamics of 3D chromatin structure across a time course of estradiol (E2) stimulation in human estrogen receptor α (ERα)-positive breast cancer cells. We identified subsets of temporally highly dynamic compartments predominantly associated with active open chromatin and found that these highly dynamic compartments showed higher alteration in tamoxifen-resistant breast cancer cells. Remarkably, these compartments are characterized by active chromatin states, and enhanced ERα binding but decreased transcription factor CCCTC-binding factor (CTCF) binding. We finally identified a set of ERα-bound promoter-enhancer looping genes enclosed within altered domains that are enriched with cancer invasion, aggressiveness or metabolism signaling pathways. This large-scale analysis expands our understanding of high-order temporal chromatin reorganization underlying hormone-dependent breast cancer.
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Project description:Three-dimensional (3D) genome spatial organization is critical for numerous cellular processes, including transcription, while certain conformation-driven structural alterations are frequently oncogenic. Genome architecture had been notoriously difficult to elucidate, but the advent of the suite of chromatin conformation capture assays, notably Hi-C, has transformed understanding of chromatin structure and provided downstream biological insights. Although many findings have flowed from direct analysis of the pairwise proximity data produced by these assays, there is added value in generating corresponding 3D reconstructions deriving from superposing genomic features on the reconstruction. Accordingly, many methods for inferring 3D architecture from proximity data have been advanced. However, none of these approaches exploit the fact that single chromosome solutions constitute a one-dimensional (1D) curve in 3D. Rather, this aspect has either been addressed by imposition of constraints, which is both computationally burdensome and cell type specific, or ignored with contiguity imposed after the fact. Here, we target finding a 1D curve by extending principal curve methodology to the metric scaling problem. We illustrate how this approach yields a sequence of candidate solutions, indexed by an underlying smoothness or degrees-of-freedom parameter, and propose methods for selection from this sequence. We apply the methodology to Hi-C data obtained on IMR90 cells and so are positioned to evaluate reconstruction accuracy by referencing orthogonal imaging data. The results indicate the utility and reproducibility of our principal curve approach in the face of underlying structural variation.
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