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

High-throughput assays of three-dimensional interactions of chromosomes have shed considerable light on the structure of animal chromatin. Despite this progress, the precise physical nature of observed structures and the forces that govern their establishment remain poorly understood. Here we present high resolution Hi-C data from early Drosophila embryos. We demonstrate that boundaries between topological domains of various sizes map to DNA elements that resemble classical insulator elements: short genomic regions sensitive to DNase digestion that are strongly bound by known insulator proteins and are frequently located between divergent promoters. Further, we show a striking correspondence between these elements and the locations of mapped polytene interband regions. We believe it is likely this relationship between insulators, topological boundaries, and polytene interbands extends across the genome, and we therefore propose a model in which decompaction of boundary-insulator-interband regions drives the organization of interphase chromosomes by creating stable physical separation between adjacent domains.

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High-resolution mapping of the three-dimensional point spread function in the near-focus region of a confocal microscope

Applied Physics Letters ◽

10.1063/1.2431764 ◽

2007 ◽

Vol 90 (3) ◽

pp. 031106 ◽

Cited By ~ 11

Author(s):

Michael J. Nasse ◽

Jörg C. Woehl ◽

Serge Huant

Keyword(s):

High Resolution ◽

Point Spread Function ◽

Three Dimensional ◽

Confocal Microscope ◽

High Resolution Mapping ◽

Point Spread ◽

Spread Function ◽

Resolution Mapping

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High-resolution mapping reveals hundreds of genetic incompatibilities in hybridizing fish species

eLife ◽

10.7554/elife.02535 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 62

Author(s):

Molly Schumer ◽

Rongfeng Cui ◽

Daniel L Powell ◽

Rebecca Dresner ◽

Gil G Rosenthal ◽

...

Keyword(s):

Gene Flow ◽

High Resolution ◽

Wide Distribution ◽

Epistatic Interactions ◽

High Resolution Mapping ◽

Swordtail Fish ◽

Genome Wide ◽

Genomic Divergence ◽

Resolution Mapping ◽

Genomic Regions

Hybridization is increasingly being recognized as a common process in both animal and plant species. Negative epistatic interactions between genes from different parental genomes decrease the fitness of hybrids and can limit gene flow between species. However, little is known about the number and genome-wide distribution of genetic incompatibilities separating species. To detect interacting genes, we perform a high-resolution genome scan for linkage disequilibrium between unlinked genomic regions in naturally occurring hybrid populations of swordtail fish. We estimate that hundreds of pairs of genomic regions contribute to reproductive isolation between these species, despite them being recently diverged. Many of these incompatibilities are likely the result of natural or sexual selection on hybrids, since intrinsic isolation is known to be weak. Patterns of genomic divergence at these regions imply that genetic incompatibilities play a significant role in limiting gene flow even in young species.

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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

10.1101/149344 ◽

2017 ◽

Cited By ~ 2

Author(s):

Michael R. Stadler ◽

Jenna E. Haines ◽

Michael B. Eisen

Keyword(s):

Drosophila Melanogaster ◽

High Resolution ◽

Polytene Chromosomes ◽

Three Dimensional ◽

Order Structure ◽

Chromatin Conformation ◽

Insulator Proteins ◽

Self Association ◽

The One ◽

Genomic Regions

AbstractEvidence 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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