Large domains of heterochromatin direct the formation of short mitotic chromosome loops

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Abstract

During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less understood. A large region of fission yeast DNA inserted into a mouse chromosome was previously observed to adopt a mitotic organisation distinct from that of surrounding mouse DNA. Here, we show that a similar distinct structure is common to a large subset of insertion events in both mouse and human cells and is coincident with the presence of high levels of heterochromatic H3 lysine nine trimethylation (H3K9me3). Hi-C and microscopy indicate that the heterochromatinised fission yeast DNA is organised into smaller chromatin loops than flanking euchromatic mouse chromatin. We conclude that heterochromatin alters chromatin loop size, thus contributing to the distinct appearance of heterochromatin on mitotic chromosomes.

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A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data.

Heng Li (2011)

Most existing methods for DNA sequence analysis rely on accurate sequences or genotypes. However, in applications of the next-generation sequencing (NGS), accurate genotypes may not be easily obtained (e.g. multi-sample low-coverage sequencing or somatic mutation discovery). These applications press for the development of new methods for analyzing sequence data with uncertainty. We present a statistical framework for calling SNPs, discovering somatic mutations, inferring population genetical parameters and performing association tests directly based on sequencing data without explicit genotyping or linkage-based imputation. On real data, we demonstrate that our method achieves comparable accuracy to alternative methods for estimating site allele count, for inferring allele frequency spectrum and for association mapping. We also highlight the necessity of using symmetric datasets for finding somatic mutations and confirm that for discovering rare events, mismapping is frequently the leading source of errors. http://samtools.sourceforge.net. hengli@broadinstitute.org.

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Organization of the mitotic chromosome.

Natalia Naumova, Maxim Imakaev, Geoffrey Fudenberg … (2013)

Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell type-specific organization described previously for nonsynchronous cells is restricted to interphase. In metaphase, we identified a homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we found that metaphase Hi-C data are inconsistent with classic hierarchical models and are instead best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.

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High-resolution TADs reveal DNA sequences underlying genome organization in flies

Fidel Ramírez, Vivek Bhardwaj, Laura Arrigoni … (2018)

Despite an abundance of new studies about topologically associating domains (TADs), the role of genetic information in TAD formation is still not fully understood. Here we use our software, HiCExplorer (hicexplorer.readthedocs.io) to annotate >2800 high-resolution (570 bp) TAD boundaries in Drosophila melanogaster. We identify eight DNA motifs enriched at boundaries, including a motif bound by the M1BP protein, and two new boundary motifs. In contrast to mammals, the CTCF motif is only enriched on a small fraction of boundaries flanking inactive chromatin while most active boundaries contain the motifs bound by the M1BP or Beaf-32 proteins. We demonstrate that boundaries can be accurately predicted using only the motif sequences at open chromatin sites. We propose that DNA sequence guides the genome architecture by allocation of boundary proteins in the genome. Finally, we present an interactive online database to access and explore the spatial organization of fly, mouse and human genomes, available at http://chorogenome.ie-freiburg.mpg.de.

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Author and article information

Contributors

Robin C Allshire:

ORCID: https://orcid.org/0000-0002-8005-3625

Gary H Karpen: Role: Reviewing Editor

Jessica K Tyler: Role: Senior Editor

Journal

Journal ID (nlm-ta): eLife

Journal ID (iso-abbrev): Elife

Journal ID (publisher-id): eLife

Title: eLife

Publisher: eLife Sciences Publications, Ltd

ISSN (Electronic): 2050-084X

Publication date (Electronic, pub): 11 September 2020

Publication date Collection: 2020

Volume: 9

Electronic Location Identifier: e57212

Affiliations

[1 ]Wellcome Centre for Cell Biology and Institute of Cell Biology, School of Biological Sciences, University of Edinburgh EdinburghUnited Kingdom

[2 ]Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School WorcesterUnited States

[3 ]Howard Hughes Medical Institute Chevy ChaseUnited States

University of California, Berkeley United States

Weill Cornell Medicine United States

University of California, Berkeley United States

University of Pennsylvania United States

Author information

Maximilian H Fitz-James http://orcid.org/0000-0002-6084-5887

Job Dekker https://orcid.org/0000-0001-5631-0698

Robin C Allshire https://orcid.org/0000-0002-8005-3625

Article

Publisher ID: 57212

DOI: 10.7554/eLife.57212

PMC ID: 7515631

PubMed ID: 32915140

SO-VID: 85a98db8-27aa-4134-b083-bfb2c46dbca0

License:

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.