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A dynamic folded hairpin conformation is associated with α-globin activation in erythroid cells

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Item Type:Article
Title:A dynamic folded hairpin conformation is associated with α-globin activation in erythroid cells
Creators Name:Chiariello, A.M. and Bianco, S. and Oudelaar, A M. and Esposito, A. and Annunziatella, C. and Fiorillo, L. and Conte, M. and Corrado, A. and Prisco, A. and Larke, M.S.C. and Telenius, J.M. and Sciarretta, R. and Musella, F. and Buckle, V.J. and Higgs, D.R. and Hughes, J.R. and Nicodemi, M.
Abstract:We investigate the three-dimensional (3D) conformations of the α-globin locus at the single-allele level in murine embryonic stem cells (ESCs) and erythroid cells, combining polymer physics models and high-resolution Capture-C data. Model predictions are validated against independent fluorescence in situ hybridization (FISH) data measuring pairwise distances, and Tri-C data identifying three-way contacts. The architecture is rearranged during the transition from ESCs to erythroid cells, associated with the activation of the globin genes. We find that in ESCs, the spatial organization conforms to a highly intermingled 3D structure involving non-specific contacts, whereas in erythroid cells the α-globin genes and their enhancers form a self-contained domain, arranged in a folded hairpin conformation, separated from intermingling flanking regions by a thermodynamic mechanism of micro-phase separation. The flanking regions are rich in convergent CTCF sites, which only marginally participate in the erythroid-specific gene-enhancer contacts, suggesting that beyond the interaction of CTCF sites, multiple molecular mechanisms cooperate to form an interacting domain.
Keywords:Globin Loci, Higher-Order Chromatin Organization, Polymer Physics, Gene Regulation, Animals, Mice
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:2125-2135
Date:18 February 2020
Official Publication:https://doi.org/10.1016/j.celrep.2020.01.044
PubMed:View item in PubMed

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