Abstract

Chromosome folding can reinforce the demarcation between euchromatin and heterochromatin. Two new studies show how epigenetic data, including DNA methylation, can accurately predict chromosome folding in three dimensions. Such computational approaches reinforce the idea of a linkage between epigenetically marked chromatin domains and their segregation into distinct compartments at the megabase scale or topological domains at a higher resolution.Please see related articles: http://dx.doi.org/10.1186/s13059-015-0741-y and http://dx.doi.org/10.1186/s13059-015-0740-z

Highlights

  • The ability to probe the spatial organization of chromosomes through the combination of chromosome conformation capture methods with high-throughput sequencing (3C–Hi-C) has revealed how chromosomes organize into active and inactive compartments [1]

  • Specific long-range contacts formed between enhancers or repressors and their cognate promoters are confined within Topological associating domains (TAD) through additional elements, named insulators or chromatin boundaries, that border

  • Insulator proteins, including CCCTCbinding factor (CTCF), bind and recruit the architectural factor cohesin that stabilizes DNA loops formed between distant elements inside TADs, thereby preventing enhancers from targeting ectopic promoters outside of such domains [3,4,5]

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Summary

Introduction

The ability to probe the spatial organization of chromosomes through the combination of chromosome conformation capture methods with high-throughput sequencing (3C–Hi-C) has revealed how chromosomes organize into active and inactive compartments (indicated ‘A’ and ‘B’ , respectively) [1]. Specific long-range contacts formed between enhancers or repressors and their cognate promoters are confined within TADs through additional elements, named insulators or chromatin boundaries, that border The three-dimensional organization of chromosomes into TADs corresponds with epigenetically defined domains that are marked by specific histone modifications [2].

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