Complex multi-enhancer contacts captured by Genome Architecture Mapping (GAM)

By R. Beagrie, Antonio Scialdone, M. Schueler, Dorothee C. A. Kraemer, Mita Chotalia, S. Q. Xie, Mariano Barbieri, Inês de Santiago, Liron-Mark Lavitas, M. Branco and 7 more. Nature, 2017

636 citations recorded by the source corpus.

The organization of the genome in the nucleus and the interactions of genes with their regulatory elements are key features of transcriptional control and their disruption can cause disease. Here we report a genome-wide method, genome architecture mapping (GAM), for measuring chromatin contacts and other features of three-dimensional chromatin topology on the basis of sequencing DNA from a large collection of thin nuclear sections. We apply GAM to mouse embryonic stem cells and identify enrichment for specific interactions between active genes and enhancers across very large genomic distances using a mathematical model termed SLICE (statistical inference of co-segregation). GAM also reveals an abundance of three-way contacts across the genome, especially between regions that are highly transcribed or contain super-enhancers, providing a level of insight into genome architecture that, owing to the technical limitations of current technologies, has previously remained unattainable. Furthermore, GAM highlights a role for gene-expression-specific contacts in organizing the genome in mammalian nuclei.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/bacba6b9c089e177607602c8f8a0836147c6b843

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Citations in the corpus

Coactivator condensation at super-enhancers links phase separation and gene control (2018, background): “Several recent studies suggest that SEs can interact with one another and may also contribute in this fashion to chromosomeorganization (55, 56).”
Targeted in situ genome-wide profiling with high efficiency for low cell numbers (2018, neutral): “By contrast, TSA-seq 32 and genome architecture mapping 33 have distance constraints and therefore measure cytological distance, either by the limited diffusion of a reactive species or the cryosectioning of cells.”
Higher-order inter-chromosomal hubs shape 3D genome organization in the nucleus (2018, methodology): “In contrast to Genome Architecture Mapping (GAM) (Beagrie et al., 2017), another Cell.”
Cohesin loss eliminates all loop domains (2017, result): “(Our findings may be related to those of other studies, which have noted enhanced interactions between higher-order intrachromosomal interactions between domains containing superenhancers (Beagrie et al., 2017).)”