Abstract

Topologically associating domains (TADs) are megabase-sized building blocks of interphase chromosomes in higher eukaryotes. TADs are chromosomal regions with increased frequency of internal interactions. On average a pair of loci separated by a given genomic distance contact each other 2–3 times more frequently when they are in the same TAD as compared to a pair of loci located in two neighbouring TADs. TADs are also functional blocks of chromosomes as enhancers and their cognate promoters are normally located in the same TAD, even if their genomic distance from each other can be as large as a megabase. The internal structure of TADs, causing their increased frequency of internal interactions, is not established yet. We survey here experimental studies investigating presence of supercoiling in interphase chromosomes. We also review numerical simulation studies testing whether transcription-induced supercoiling of chromatin fibres can explain how TADs are formed and how they can assure very efficient interactions between enhancers and their cognate promoters located in the same TAD.

Highlights

  • From topological domains to Topologically associating domains (TADs)Many of us are familiar with the famous dictum attributed to Jacques Monod ‘Anything found to be true of Escherichia coli must be true of elephants’ [1]

  • We discussed here experimental data supporting the notion that TADs are supercoiled

  • We presented how supercoiling of chromatin fibres can be generated during transcription and how supercoiling is expected to induce compaction of individual TADs and promote interaction between enhancers and their cognate promoters that are located in the same TAD

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Summary

Introduction

From topological domains to TADsMany of us are familiar with the famous dictum attributed to Jacques Monod ‘Anything found to be true of Escherichia coli must be true of elephants’ [1]. In a biological setting where enhancers show affinity to promoters and where electrostatic repulsion between chromatin regions is largely screened, the supercoiling of chromosomal loops forming TADs can guarantee high fidelity of enhancer promoter interactions even if on average the contacts between generic sites located in the same TAD are only 2–3 times

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