Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
The three-dimensional configuration of the genome is complex, dynamic and crucial for gene regulation. In the past few years, technological advances in chromosome conformation capture methods and in microscopy techniques revealed how the organization of the genome is interconnected with nuclear architecture and can vary between cell types and during cell differentiation and development. This collection includes recent articles from across the Nature group of journals and showcases both the latest advances in the methodologies used to study genome organization, and our recent understanding of how genome organization and nuclear architecture regulate gene expression, cell fate and cell function in physiology and disease. The content of this collection has been chosen by the editors of Nature Reviews Molecular Cell Biology.
How chromosomes are positioned and folded within the nucleus has implications for gene regulation. In this Review, Kempfer and Pombo describe and evaluate methods for studying chromosome architecture and outline the insights they are providing about nuclear organization.
Different genomic regions are replicated at different times during the S phase of the cell cycle, forming early- and late-replicating domains that occupy different locations in the nucleus. The recent identification of specific DNA sequences and long non-coding RNAs that regulate DNA replication timing is providing key insights into the roles of replication timing and into timing and 3D organization.
The 3D organization of the genome is crucial for gametogenesis, embryogenesis and cell differentiation through its modulation of transcription, DNA replication and cell division. Recent studies have highlighted the roles of 3D chromatin dynamics, such as the formation of enhancer–promoter interactions in mammalian development.
For appropriate control of gene expression, enhancers must communicate with the right target genes at the right time, typically over large genomic distances. In this Review, Schoenfelder and Fraser discuss our latest understanding of long-range enhancer–promoter crosstalk, including target-gene specificity, interaction dynamics, protein and RNA architects of interactions, roles of 3D genome organization and the pathological consequences of regulatory rewiring.
Genome organization can regulate gene expression, but can gene expression regulate genome organization? Recent studies reveal that, although not required for higher-level genome organization, transcription has a role in the formation and stabilization of genomic subdomains and enhancer–promoter interactions.
High-resolution studies of chromosome conformation are revealing that the 3D genome is organized into smaller structural features than was previously supposed and is primarily composed of compartmental domains and CTCF loops. In this Perspectives article Rowley and Corces describe the latest views on the organizational drivers and principles of the 3D genome, and the interplay between genome activity and organization.
Mechanical cues from the microenvironment can be efficiently transmitted to the nucleus to engage in the regulation of genome organization and gene expression. Recent technological and theoretical progress sheds new light on the relationships between cell mechanics, nuclear and chromosomal architecture and gene transcription.
This Review summarizes our understanding of plant chromatin organization and positioning beyond the nucleosomal level, advanced by up-to-date chromatin conformation capture methods and visualization techniques, as well as discusses future directions.
The three-dimensional (3D) organization of eukaryote chromosomes regulates genome function and nuclear processes such as DNA replication, transcription and DNA-damage repair. Experimental and computational methodologies for 3D genome analysis have been rapidly expanding, with a focus on high-throughput chromatin conformation capture techniques and on data analysis.
Recent studies show that structural variation can alter the genome architecture, leading to changes in the regulation of gene expression that cause disease. The authors review the role of genetic structural variation in disease and the pathogenic potential of changes to the 3D genome.
The 4D Nucleome Network aims to map the spatial and dynamic organization of the human and mouse genomes to gain insight into the structure and biological functions of the nucleus.
In this Review, the authors compare commonly used chromosome conformation capture techniques, describing their respective strengths and weaknesses, and provide advice for the end user on which approach and analysis method to use.
Mechanistic insights are emerging into how long non-coding RNAs (lncRNAs) regulate gene expression by coordinating regulatory proteins, localizing to genomic loci and shaping nuclear organization. Interestingly, lncRNAs can perform functions that cannot be carried out by DNA elements or proteins alone, such as amplifying regulatory signals in the nucleus.
Three-dimensional genome organization can shape gene expression by facilitating interactions between regulatory elements. The authors review the process of X-chromosome inactivation with a focus on chromatin organization and subnuclear localization of the active and inactive X chromosomes, as well as the potential roles of long non-coding RNAs.
Mutations in non-coding parts of the genome can cause disease. Technological advances are providing unprecedented detail on genome organization and folding, and have revealed that enhancer–target gene coupling is spatially restricted, as it occurs within topologically associated domains (TADs), and that disrupting such organization can lead to disease-associated gene dysregulation.
Job Dekker asserts that cases in which data from microscopy- and 3C-based methods appear discordant about genome organization will provide opportunities to improve our models of chromatin folding.
Genome-wide mapping of chromatin contacts reveals the structural and organizational changes that the metazoan genome undergoes during cell differentiation. These changes involve entire chromosomes, which are influenced by contacts with nuclear structures such as the lamina, and local interactions mediated by transcription factors and chromatin looping.
In this article the authors review current knowledge on chromatin architecture and the molecular mechanisms that underlie it. They discuss how three-dimensional (3D) organization of chromatin relates to gene expression, development and disease, and consider its effect on genome evolution.
Synthetic biology approaches to characterize gene regulation have largely used transcription factor circuits in bacteria. However, the multilayered regulation of genes by chromatin in eukaryotes provides opportunities for more sophisticated control of gene expression. This Review describes diverse approaches for engineering eukaryotic chromatin states, the insights gained into physiological gene regulation principles, and the broad potential applications throughout biomedical research and industry.
The evolution of genes is influenced by regional variation in mutation rates (RViMR). Chromatin organization affects RViMR, although the correlation between chromatin state and mutation types and rates is complex. This Review describes recent research on RViMR and chromatin organization, and the emerging findings from investigations of both germline and somatic mutations.
Promoter–enhancer loopings and other features of the 3D genome are dynamically regulated in the brain. In this Review, Akbarian and colleagues discuss how neuronal and glial gene expression is governed by the 3D genome, with implications for cognition and neuropsychiatric disease.