A Three-Dimensional Model of the Yeast Genome

By Z. Duan, Mirela Andronescu, K. Schutz, Sean J. Mcllwain, Y. Kim, Choli Lee, Jay Shendure, Stanley Fields, C. Blau, William Stafford Noble. Nature, 2010

1,004 citations recorded by the source corpus.

Layered on top of information conveyed by DNA sequence and chromatin are higher order structures that encompass portions of chromosomes, entire chromosomes, and even whole genomes. Interphase chromosomes are not positioned randomly within the nucleus, but instead adopt preferred conformations. Disparate DNA elements co-localize into functionally defined aggregates or ‘factories’ for transcription and DNA replication. In budding yeast, Drosophila and many other eukaryotes, chromosomes adopt a Rabl configuration, with arms extending from centromeres adjacent to the spindle pole body to telomeres that abut the nuclear envelope. Nonetheless, the topologies and spatial relationships of chromosomes remain poorly understood. Here we developed a method to globally capture intra- and inter-chromosomal interactions, and applied it to generate a map at kilobase resolution of the haploid genome of Saccharomyces cerevisiae. The map recapitulates known features of genome organization, thereby validating the method, and identifies new features. Extensive regional and higher order folding of individual chromosomes is observed. Chromosome XII exhibits a striking conformation that implicates the nucleolus as a formidable barrier to interaction between DNA sequences at either end. Inter-chromosomal contacts are anchored by centromeres and include interactions among transfer RNA genes, among origins of early DNA replication and among sites where chromosomal breakpoints occur. Finally, we constructed a three-dimensional model of the yeast genome. Our findings provide a glimpse of the interface between the form and function of a eukaryotic genome.

Subfields: Genetics, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/7fff02ac8d7fee38d6277afeee61e024d6454c72

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Citations in the corpus

Heterogeneous substitution systems revisited (2016, neutral): “Conventional optimization or standard deep reinforcement learning (DRL) methods struggle with convergence and exploration in such environments, especially when access and backhaul links are tightly coupled, making scalable and robust solutions elusive.”
Chromosome-scale scaffolding of de novo genome assemblies based on chromatin interactions (2013, methodology): “HiC and related protocols use proximity ligation and massively parallel sequencing to probe the threedimensional architecture of chromosomes within the nucleus, with interacting regions captured to pairedend reads 17,18 .”
Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data (2013, methodology): “Other 3C variants have recently been described that differ in molecular details but that all generate comprehensive and genome‑wide interaction maps 28,47,57,75 .”
Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts (2014, methodology): “To calculate statistical confidence estimates for inter-chromosomal contacts, Duan et al. (2010) used a uniform probability model to evaluate the probability of observing a contact countof k ‘ 1 ;‘ 2 forloci ‘ 1 and ‘ 2 .”
Three-dimensional folding and functional organization principles of the Drosophila genome. (2012, methodology): “…of 3C made use of high-throughput sequencing to globally map chromatin contacts in human (Lieberman-Aiden et al., 2009; the Hi-C method) and yeast (Duan et al., 2010; Tanizawa et al., 2010), or of subsets of genomic interactions between regions bound by regulatory factors (Fullwood et al., 2009;…”
Mapping nucleosome resolution chromosome folding in yeast by Micro-C (2015, neutral): “in Yeast by Micro-C”