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Architectural alterations in enhancer repertoires orchestrate senescence-associated secretory phenotype profile [ChIP-seq]

ABSTRACT: The emerging 4D genome project aiming to map the dynamics of genomes in spatial and temporal dimension has put forward to developing the mechanisms of how the nucleus is organized and functions. Therefore, processes like cellular senescence characterized by complex events give rise to understanding the regulation network from 1D genome to dynamically organized 3D structure. Unfortunately, how spatial genome reorganization triggers cellular senescence and how it influences senescence-related downstream transcriptional profile remains unaddressed well. Here, we uncover that re re-orchestration of 3D chromatin architecture has occurred in cellular senescence, accompanied with remodeling of enhancer repertories, which in turn facilicate the recruitment of the chromatin reader C/EBPα to newly activated senescence enhancers (SAEs), leading to the expression of SAEs flanking SASP genes kinetics.

ORGANISM(S): Mus musculus

PROVIDER: GSE117209 | GEO | 2018/07/18

REPOSITORIES: GEO

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Architectural alterations in enhancer repertoires orchestrate senescence-associated secretory phenotype profile [RNA-seq]

Project description:The emerging 4D genome project aiming to map the dynamics of genomes in spatial and temporal dimension has put forward to developing the mechanisms of how the nucleus is organized and functions. Therefore, processes like cellular senescence characterized by complex events give rise to understanding the regulation network from 1D genome to dynamically organized 3D structure. Unfortunately, how spatial genome reorganization triggers cellular senescence and how it influences senescence-related downstream transcriptional profile remains unaddressed well. Here, we uncover that re re-orchestration of 3D chromatin architecture has occurred in cellular senescence, accompanied with remodeling of enhancer repertories, which in turn facilicate the recruitment of the chromatin reader C/EBPα to newly activated senescence enhancers (SAEs), leading to the expression of SAEs flanking SASP genes kinetics.

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Architectural alterations in enhancer repertoires orchestrate senescence-associated secretory phenotype profile [Hi-C]

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Redistribution of the Lamin B1 genomic binding profile affects spatial rearrangement of heterochromatic domains and gene expression during senescence

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Engineering Extracellular Vesicles by Three-dimensional Dynamic Culture of Human Mesenchymal Stem Cells

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Redistribution of the Lamin B1 genomic binding profile affects spatial rearrangement of heterochromatic domains and gene expression during senescence

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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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