Search

Here, the authors find that BMAL1, best known for controlling the body clock, partners with TRIM28 in naïve pluripotent stem cells to repress retrotransposons.

Single-cell comparison of developing bat and mouse limbs reveals conservation of cell populations and gene expression patterns, and suggests repurposing of genes involved in proximal limb development for wing evolution.

The physical organization of the genome in non-bilaterian animals and their closest unicellular relatives is characterized; comparative analysis shows chromatin looping is a conserved feature of genome architecture and spatial genome regulation emerged early in animal evolution.

The dynamics of genome architecture during human cell differentiation and upon neoplastic transformation remain poorly characterized. Here, the authors integrate in situ Hi-C and nine additional omic layers to characterize the dynamic changes in 3D genome architecture during normal B cell differentiation and in neoplastic cells from chronic lymphocytic leukemia and mantle cell lymphoma patients.

Regulation of chromosome structure plays essential roles in many nuclear processes. Here, the authors present TADdyn, a tool that integrates time-course 3C data, restraint-based modelling, and molecular dynamics to simulate the structural rearrangements of genomic loci and find that during gene activation, transcription starting sites contact with open chromatin regions into active physical domains.

OligoFISSEQ combines Oligopaints with fluorescence in situ sequencing to enable the 3D mapping of many regions across the genome in human cells to interrogate genome organization at improved genomic resolution. OligoFISSEQ is compatible with immunochemistry and OligoSTORM for super-resolution imaging.

Deconwolf is a computationally efficient and user-friendly software tool for fluorescence microscopy image deconvolution that improves the analysis of diverse fluorescence in situ hybridization methods and can handle large datasets.

The three-dimensional organization of genomes can now be explored at increased resolution using approaches based on 3C technology. This Review discusses how these chromatin interaction data sets can be interpreted using statistical approaches and computational modelling, and considers the levels of organization that are revealed.

Analysis of Hi-C datasets is limited by the current existing methods for data normalization, with detection of features such as TADs and chromatin loops being inconsistent amongst different approaches. Here the authors develop Binless, a method that allows for reproducible normalization of Hi-C data independent of its resolution and compare how Binless performs in comparison with other methods.

How mammalian genomes are packaged and the heritability of structural variations in genome folding is incomplete. Here, the authors investigate the impact of chromosomal fusions on three-dimensional genome topology and meiotic recombination, highlighting the implications of large-scale genome reorganizations on genome function, evolution, and fertility.

Chromatin structure and topology play important roles in the regulation of gene expression. Here the authors study the spatio-temporal re-organization of promoter-enhancer interactions in pluripotent ES and skeletal muscle stem cells and the corresponding impact on gene expression as a consequence of myogenic commitment and differentiation.

The colocation of all RNAs in the nucleus is determined with a droplet sequencing method.

Here the authors computationally test the hypothesis that RNA organizes the three-dimensional genome via a triplex-forming mechanism, providing evidence that lncRNA-targeted triplex hotspots can contribute to large-scale chromosome compartmentalization.

Analysis of bivalent promoters in embryonic stem cells (ESCs) shows that deletion of MLL2 in ESCs leads to increased Polycomb occupancy, reduced promoter accessibility, redistribution of long-range chromatin interactions, and failure to differentiate.

Depletion, ChIP and Hi-C analyses of the genomic distribution of the two variant cohesin complexes in human cells reveal non-redundant functions and differential contributions to 3D genome organization.

Promoter capture Hi-C maps in human pancreatic islets identify more than 1,300 three-dimensional regulatory hubs, linking diabetes-associated enhancers to their target genes. Genetic variation in hubs impacts insulin secretion heritability.

The three-dimensional architecture of genome-reduced bacteria is poorly understood. Here the authors combine Hi-C with super-resolution microscopy inMycoplasma pneumoniaeand provide evidence of how supercoiling and local organization influences gene regulation.

Eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that exist at the kilo-megabase scale. Here Cattoni et al. combine super-resolution microscopy with DNA-labeling methods to quantify absolute frequencies of interactions within TADs.

The authors analyze time-resolved changes in genome topology, gene expression, transcription-factor binding, and chromatin state during iPSC generation. They conclude that 3D genome reorganization generally precedes gene expression changes and that removal of locus-specific topological barriers explains why pluripotency genes are activated sequentially during reprogramming.

Lamina-associated domains (LADs) contact lamins in the nuclear lamina, and lamin B1 was thought to bind heterochromatic regions at the nuclear envelope. Here, the authors show lamin B1 associates with actively expressed euchromatin regions, creating dynamic euchromatin lamina-associated domains (eLADs) during epithelial-to-mesenchymal transition.

A study applies polymer physics to assess the advantages and limitations of three sequencing-based approaches for determining the structure of genomes and genomic domains.

Genomes are highly organized in space and time. Compartments, topologically associating domains (TADs) and loops are three dimensional (3D) genome features that have been extensively studied. Among these three levels of organization, TADs have sparked the most debate. New microscopy data shed light on how TADs and their leaky borders contribute to gene regulation.

The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe.

CHESS is an algorithm that compares chromatin contact maps and identifies differential features. It can analyze interspecies syntenic regions and three-dimensional changes caused by genetic perturbation.

An integrated resource of (epi)genomic features in annotated chronic lymphocytic leukemia (CLL) primary samples uncovers subgroup-specific regulatory alterations associated with clinical behavior.

CTCF is dispensable for transdifferentiation of B cells into induced macrophages despite widespread loss of topologically associating domains. CTCF depletion impairs upregulation of inflammatory genes after endotoxin exposure by destabilizing promoter–enhancer interactions.

Understanding genomic organization in three dimensions may be one key to understanding gene regulation. Through the combination of an advanced version of chromosome conformation capture technology and an integrated modeling platform, the structure of the α-globin locus in cells where it is silent is compared to that in cells with high α-globin expression.