Comparative Hi-C Reveals that CTCF Underlies Evolution of Chromosomal Domain Architecture

By Matteo Vietri Rudan, Christopher Barrington, S. Henderson, Christina Ernst, Duncan T. Odom, Amos Tanay, Suzana Hadjur. Cell Reports, 2015

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Summary Topological domains are key architectural building blocks of chromosomes, but their functional importance and evolutionary dynamics are not well defined. We performed comparative high-throughput chromosome conformation capture (Hi-C) in four mammals and characterized the conservation and divergence of chromosomal contact insulation and the resulting domain architectures within distantly related genomes. We show that the modular organization of chromosomes is robustly conserved in syntenic regions and that this is compatible with conservation of the binding landscape of the insulator protein CTCF. Specifically, conserved CTCF sites are co-localized with cohesin, are enriched at strong topological domain borders, and bind to DNA motifs with orientations that define the directionality of CTCF’s long-range interactions. Conversely, divergent CTCF binding between species is correlated with divergence of internal domain structure, likely driven by local CTCF binding sequence changes, demonstrating how genome evolution can be linked to a continuous flux of local conformation changes. We also show that large-scale domains are reorganized during genome evolution as intact modules.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/7a44e41c18a16c6498ee212be742b781f886bec2

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Citations in the corpus

Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization (2017, neutral): “Strikingly, in most of the cases, a pair of CTCF sites only engage in contact above local background if they are in a convergent linear orientation (Rao et al., 2014), creating an asymmetry in the insulation pattern (Vietri Rudan et al., 2015).”
CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function (2015, positive): “This organization of CBS sites within the Pcdh clusters was recently shown to reflect the genome-wide organization of CBS pairs at anchors of DNA contact loops (Alt et al., 2013; Rao et al., 2014; Vietri Rudan et al., 2015).”
Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins (2017, positive): “However, high-resolution genome-wide chromatin conformation capture experiments coupled with DNA sequencing (“Hi-C”) (Lieberman-Aiden et al, 2009) have revealed that most chromatin loops contain convergent CTCF sites (Rao et al, 2014; Vietri Rudan et al, 2015; de Wit et al, 2015).”
Genomic positional conservation identifies topological anchor point (tap)RNAs linked to developmental loci (2016, background): “This is especially relevant given the robust conservation of chromatin conformation in syntenic regions, in which conserved CTCF-Cohesin binding sites are enriched at the borders of topological domains (Vietri Rudan et al., 2015).”
Ever-changing landscapes: transcriptional enhancers in development and evolution (2016, background): “Strikingly, TAD boundaries appear to be largely invariant between cell types and are conserved across even distantly related species, suggesting that TADs represent a fixed structural unit of chromatin organization within which tissue-specific regulatory interactions can occur and evolve (Dixon et a”
A Compendium of Chromatin Contact Maps Reveal Spatially Active Regions in the Human Genome (2016, neutral): “Introduction Chromosome conformation capture (3C)-based techniques have begun to reveal molecular details of nuclear organization in eukaryotic cells (Dekker et al., 2002; Dixon et al., 2012, 2015; Dostie et al., 2006; Fraser et al., 2015; Jin et al., 2013; Lieberman-Aiden et al., 2009; Rao et al., ”