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Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the early Drosophila melanogaster embryo

View ORCID ProfileMichael R. Stadler, Jenna E. Haines, View ORCID ProfileMichael B. Eisen
doi: https://doi.org/10.1101/149344
Michael R. Stadler
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA
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Jenna E. Haines
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA
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Michael B. Eisen
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA
2 Department of Integrative Biology, University of California, Berkeley, CA
3 Howard Hughes Medical Institute, University of California, Berkeley, CA
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Abstract

Evidence has emerged in recent years linking insulators and the proteins that bind them to the higher order structure of animal chromatin, but the precise nature of this relationship and the manner by which insulators influence chromatin structure have remained elusive. Here we present high-resolution genome-wide chromatin conformation capture (Hi-C) data from early Drosophila melanogaster embryos that allow us to map three-dimensional interactions to 500 base pairs. We observe a complex, nested pattern of regions of chromatin self-association, and use a combination of computational and manual annotation to identify boundaries between these topological associated domains (TADs). We demonstrate that, when mapped at high resolution, boundaries resemble classical insulators: short (500 - 1000 bp) genomic regions that are sensitive to DNase digestion and strongly bound by known insulator proteins. Strikingly, we show that for regions where the banding pattern of polytene chromosomes has been mapped to genomic position at comparably high resolution, there is a perfect correspondence between polytene banding and our chromatin conformation maps, with boundary insulators forming the interband regions that separate compacted bands that correspond to TADs. We propose that this precise, high-resolution relationship between insulators and TADs on the one hand and polytene bands and interbands on the other extends across the genome, and suggest a model in which the decompaction of insulator regions drives the organization of interphase chromosomes by creating stable physical separation between adjacent domains.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 13, 2017.
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Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the early Drosophila melanogaster embryo
Michael R. Stadler, Jenna E. Haines, Michael B. Eisen
bioRxiv 149344; doi: https://doi.org/10.1101/149344
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Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the early Drosophila melanogaster embryo
Michael R. Stadler, Jenna E. Haines, Michael B. Eisen
bioRxiv 149344; doi: https://doi.org/10.1101/149344

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