Hierarchical role for transcription factors and chromatin structure in genome organization along adipogenesis.

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However, given the multitude of chromatin-associating factors, the mechanisms driving the colocalization of active chromosomal domains and the role of this organization in regulating the transcription program in adipocytes are not clear. Analysis of genome-wide chromosomal associations revealed cell type-specific spatial clustering of adipogenic genes in 3T3-L1 cells. Time course analysis demonstrated that the adipogenic 'hub', sampled by PPARγ and Lpin1, undergoes orchestrated reorganization during adipogenesis. Coupling the dynamics of genome architecture with multiple chromatin datasets indicated that among all the transcription factors (TFs) tested, RXR is central to genome reorganization at the beginning of adipogenesis. Interestingly, at the end of differentiation, the adipogenic hub was shifted to an H3K27me3-repressive environment in conjunction with attenuation of gene transcription. We propose a stage-specific hierarchy for the activity of TFs contributing to the establishment of an adipogenic genome architecture that brings together the adipogenic genetic program. In addition, the repositioning of this network in a H3K27me3-rich environment at the end of differentiation may contribute to the stabilization of gene transcription levels and reduce the developmental plasticity of these specialized cells.\nDATABASE: All sequence data reported in this paper have been deposited at GEO (http://www.ncbi.nlm.nih.gov/geo/) (GSE92475).", "claims": [{"id": "claim-target-result", "statement": "The study used 4C-seq with hypergeometric testing for contact-region overlap and found that the adipogenic loci PPARγ and Lpin1 undergo coordinated genome reorganization during adipogenesis, with RXR central to early reorganization; the sequence data were deposited in GEO under accession GSE92475.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:28755519", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Time course analysis demonstrated that the adipogenic \"hub\", sampled by PPARγ and Lpin1, undergoes orchestrated reorganization during adipogenesis."}, {"asset": "source:pmid:28755519", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Coupling the dynamics of genome architecture with multiple chromatin datasets indicated that among all the transcription factors tested, RXR is central to genome reorganization at the beginning of adipogenesis."}, {"asset": "source:pmid:28755519", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Inter-chromosomal associations shared by the adipogenic genesPPARγ and Lpin1, while distinct from the compartment of the non-adipogenic gene Ifng."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study used 4C-seq with hypergeometric testing for contact-region overlap and found that the adipogenic loci PPARγ and Lpin1 undergo coordinated genome reorganization during adipogenesis, with RXR central to early reorganization; the sequence data were deposited in GEO under accession GSE92475.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:28755519"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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