Review Article | Published:

The role of transcription in shaping the spatial organization of the genome

Abstract

The spatial organization of the genome into compartments and topologically associated domains can have an important role in the regulation of gene expression. But could gene expression conversely regulate genome organization? Here, we review recent studies that assessed the requirement of transcription and/or the transcription machinery for the establishment or maintenance of genome topology. The results reveal different requirements at different genomic scales. Transcription is generally not required for higher-level genome compartmentalization, has only moderate effects on domain organization and is not sufficient to create new domain boundaries. However, on a finer scale, transcripts or transcription does seem to have a role in the formation of subcompartments and subdomains and in stabilizing enhancer–promoter interactions. Recent evidence suggests a dynamic, reciprocal interplay between fine-scale genome organization and transcription, in which each is able to modulate or reinforce the activity of the other.

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Acknowledgements

The authors thank members of their laboratories, E. de Wit and anonymous reviewers for helpful comments. B.v.S. and E.E.M.F. are supported by European Research Council (ERC) Advanced Grants, GoCADiSC (694466) and DeCRyPT (787611), respectively. The Oncode Institute is supported by KWF Dutch Cancer Society.

Reviewer information

Nature Reviews Molecular Cell Biology thanks B. Bruneau, G. Almouzni and other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

The authors contributed equally to all aspects of the article.

Competing interests

The authors declare no competing interests.

Correspondence to Bas van Steensel or Eileen E. M. Furlong.

Glossary

Alu elements

A type of short and highly abundant transposable element found throughout primate genomes.

Histone modifications

A generic term for a wide range of post-translational modifications of histone residues. Histone modifications have a variety of functions, including in the packaging of chromatin and regulation of transcription.

Nuclear lamina

A layer of proteins coating the inner nuclear membrane and thought to form a large contact surface for lamina-associated domains.

CCCTC-binding factor

(CTCF). A DNA-binding protein that often marks borders of lamina-associated domains, topologically associated domains and chromatin loops and can act as a transcriptional insulator.

Hi-C

A chromosome conformation capture method that systematically identifies genomic sequences that are in close proximity to one another inside cell nuclei.

Super enhancers

A somewhat arbitrary definition of genomic regions that contain a high density of active enhancers.

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Fig. 1: Two main principles of chromosome organization.
Fig. 2: Gene relocalization from peripheral heterochromatin to internal euchromatin.
Fig. 3: Alternative mechanisms of TAD boundary formation.
Fig. 4: Properties of TAD borders in different cell types and species.
Fig. 5: Compartmentalization of active and inactive chromatin.