CTCF-mediated transcriptional regulation through cell type-specific chromosome organization in the β-globin locus.Report as inadecuate




CTCF-mediated transcriptional regulation through cell type-specific chromosome organization in the β-globin locus. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 ISC-PIF - Institut des Systèmes Complexes - Paris Ile-de-France 2 CRG-UPF - Center for Genomic Regulation 3 LCDB - Laboratory of Cellular and Developmental Biology 4 Génopole Evry

Abstract : The principles underlying the architectural landscape of chromatin beyond the nucleosome level in living cells remains largely unknown despite its potential to play a role in mammalian gene regulation. We investigated the three-dimensional folding of a 1 Mbp region of human chromosome 11 containing the β-globin genes by integrating looping interactions of the CCCTC-binding insulator protein CTCF determined comprehensively by chromosome conformation capture 3C into a polymer model of chromatin. We find that CTCF-mediated cell type-specific interactions in erythroid cells are organized to favor contacts known to occur in vivo between the β-globin locus control region LCR and genes. In these cells, the modeled β-globin domain folds into a globule with the LCR and the active globin genes on the periphery. In contrast, in non-erythroid cells, the globule is less compact with few but dominant CTCF interactions driving the genes away from the LCR. This leads to a decrease in contact frequencies that can exceed 1000-fold depending on the stiffness of the chromatin and the exact position of the genes. Our findings show that an ensemble of CTCF contacts functionally affects spatial distances between control elements and target genes contributing to chromosomal organization required for transcription.





Author: Ivan Junier - Ryan K Dale - Chunhui Hou - François Képès - Ann Dean -

Source: https://hal.archives-ouvertes.fr/



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