title: Topologically Associating Domains: An invariant framework or a dynamic scaffold?
abstract: Metazoan genomes are organized into regions of topologically associating domains (TADs). TADs are demarcated by border elements, which are enriched for active genes and high occupancy architectural protein binding sites. We recently demonstrated that 3D chromatin architecture is dynamic in response to heat shock, a physiological stress that downregulates transcription and causes a global redistribution of architectural proteins. We utilized a quantitative measure of border strength after heat shock, transcriptional inhibition, and architectural protein knockdown to demonstrate that changes in both transcription and architectural protein occupancy contribute to heat shock-induced TAD dynamics. Notably, architectural proteins appear to play a more important role in altering 3D chromatin architecture. Here, we discuss the implications of our findings on previous studies evaluating the dynamics of TAD structure during cellular differentiation. We propose that the subset of variable TADs observed after differentiation are representative of cell-type specific gene expression and are biologically significant.
authors.affiliation: a Department of Biology ; Emory University ; Atlanta , GA USA.
authors.forename: Caelin
authors.initials: C
authors.lastname: Cubeñas-Potts
authors.affiliation: a Department of Biology ; Emory University ; Atlanta , GA USA.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Corces
mesh_terms: D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D016678:Genome; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D013312:Stress, Physiological; D013696:Temperature
chemical_list: D000076246:CCCTC-Binding Factor; D002843:Chromatin; D011506:Proteins; D012097:Repressor Proteins
keywords: 3D architecture; CTCF; TAD; architectural proteins; chromatin; differentiation; epigenetics; heat shock; insulators