Juicer Provides a One-Click System for Analyzing Loop-Resolution Hi-C Experiments

Durand, Neva C.; Shamim, Muhammad S.; Machol, Ido; Rao, Suhas S.P.; Huntley, Miriam; Lander, Eric S.; Aiden, E

doi:10.1016/j.cels.2016.07.002

Cited by 2,228 publications

(2,050 citation statements)

References 9 publications

Supporting

Mentioning

2,031

Contrasting

Unclassified

Order By: Relevance

“…Smchd1 has well characterised roles in developmental gene silencing in both mouse and human 12,[21][22][23]25,56,57 . In this study we have implicated Smchd1 in the developmental silencing of another fundamentally important set of genes, the Hox cluster genes.…”

Section: Discussionmentioning

confidence: 99%

“…We first identified Smchd1 based on its role in repeat-induced silencing in mice 12,20 , and it also plays an important role in silencing the D4Z4 macrosatellite repeat in humans 21 . Smchd1 has a critical role in silencing the inactive X (Xi) chromosome in females 12,22 , and in transcriptional repression of specific autosomal loci, including select imprinted genes and the clustered protocadherins 17,[23][24][25] . Each of these sites are direct targets of Smchd1 12,17,26 , but interestingly so are other autosomal loci including the Hox genes 17 , where the role of Smchd1 has not been explored.…”

Section: Introductionmentioning

confidence: 99%

“…Smchd1 null females die around embryonic day 10.5 (E10.5), with failed X inactivation 12,22,23,25 . In these embryos the early stages of X inactivation proceed normally; however, by mid-gestation failed X-linked gene silencing is accompanied by DNA hypomethylation of a subset of CpG islands on .…”

Section: Introductionmentioning

confidence: 99%

“…8, 2018; 5 the Xi 12,22 . The absence of SMCHD1 is also associated with DNA hypomethylation at its autosomal targets 17,21,25,27 . While these epigenetic changes have helped to place Smchd1 Here we tested whether Smchd1 has a role in maintaining chromosome structure using in situ chromosome conformation capture followed by sequencing (in situ Hi-C).…”

mentioning

confidence: 99%

“…The absence of SMCHD1 is also associated with DNA hypomethylation at its autosomal targets 17,21,25,27 . While these epigenetic changes have helped to place Smchd1 somewhere upstream of DNA methylation in the ontogeny of gene silencing, they have not revealed how Smchd1 functions to enable transcriptional repression.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Long-range chromatin interactions on the inactive X and atHoxclusters are regulated by the non-canonical SMC protein Smchd1

Jansz

Keniry

Trussart

et al. 2018

Preprint

View full text Add to dashboard Cite

The regulation of higher order chromatin structure is complex and dynamic; however we do not yet understand the full suite of mechanisms governing architecture. Here we reveal the noncanonical SMC protein Smchd1 as a novel regulator of long-range chromatin interactions, and add it to the canon of epigenetic proteins required for Hox gene regulation. The effect of losing Smchd1-dependent chromatin interactions has varying outcomes dependent on chromatin context. At autosomal targets transcriptionally sensitive to Smchd1 deletion, we find increased short-range interactions and ectopic enhancer activation. By contrast, the inactive X chromosome is transcriptionally refractive to Smchd1 ablation, despite chromosome-wide increases in shortrange interactions. There we observe spreading of H3K27me3 domains into regions not normally decorated by this mark. Together these data suggest Smchd1 has the capacity to insulate the chromatin, thereby limiting access to other chromatin modifying proteins.. CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/342212 doi: bioRxiv preprint first posted online Jun. 8, 2018; 3 In recent years there has been a dramatic increase in our understanding of how DNA forms longrange interactions [1][2][3][4] . This is largely due to chromatin conformation capture and sequencing (Hi-C) techniques, which have been used to map chromatin contacts genome-wide 5,6 . Hi-C revealed the presence of topologically associated domains (TADs): Mb-sized self-interacting regions 7 . As these techniques increased in resolution, they also enabled study of chromosome looping.However, our knowledge of these genomic structures has far preceded an understanding of mechanism and function.As Hi-C data revealed the ways in which DNA molecules are spatially organised within the nucleus, models were developed to explain the mechanism by which chromatin structures could be formed and maintained. The model with the most traction has been the loop extrusion model, in which DNA extrudes through a ring formed by the SMC complex, Cohesin, until the complex is stabilised by convergent Ctcf binding at TAD boundaries. As such, Ctcf and Cohesin have been the focus of much research in the field. However, genome-wide loss of Ctcf and Cohesin mediated structures often have a surprisingly limited effect on transcription 8,9 . It is known that a host of epigenetic regulators are also involved in the formation and maintenance of higher order chromatin structures that modulate transcription. This is exemplified by polycomb repressive complex 1 (PRC1), which is involved in forming long-range repressive chromatin interactions that are distinct from TADs, and which result in compaction of the locus 10,11 . Continued identification of epigenetic regulators that mediate long-range chromatin interactions will help to resolve t...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Long-range chromatin interactions on the inactive X and atHoxclusters are regulated by the non-canonical SMC protein Smchd1

Jansz

Keniry

Trussart

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

Circular Trajectory Reconstruction Uncovers Cell‐Cycle Progression and Regulatory Dynamics from Single‐Cell Hi‐C Maps

Gao

Zhang

2019

Advanced Science

View full text Add to dashboard Cite

Single‐cell Hi‐C technology is emerging and will provide unprecedented opportunities to elucidate chromosomal dynamics with high resolution. How to characterize pseudo time‐series of single cells using single‐cell Hi‐C maps is an essential and challenging topic. To this end, a powerful circular trajectory reconstruction tool CIRCLET is developed to resolve cell cycle phases of single cells by considering multiscale features of chromosomal architectures without specifying a starting cell. CIRCLET reveals its best superiority based on the combination of one feature set about global information and another two feature sets about local interactional information in terms of designed evaluation indexes and verification strategies from a collection of cell‐cycle Hi‐C maps of 1171 single cells. Further division of the reconstructed trajectory into 12 stages helps to accurately characterize the dynamics of chromosomal structures and explain the special regulatory events along cell‐cycle progression. Last but not the least, the reconstructed trajectory helps to uncover important regulatory genes related with dynamic substructures, providing a novel framework for discovering regulatory regions even cancer markers at single‐cell resolution.

show abstract

Dynamic Interplay between Structural Variations and 3D Genome Organization in Pancreatic Cancer

et al. 2022

Advanced Science

View full text Add to dashboard Cite

Structural variations (SVs) are the greatest source of variations in the genome and can lead to oncogenesis. However, the identification and interpretation of SVs in human cancer remain technologically challenging. Here, long-read sequencing is first employed to depict the signatures of structural variations in carcinogenesis of human pancreatic ductal epithelium. Then widespread reprogramming of the 3D chromatin architecture is revealed by an in situ Hi-C technique. Integrative analyses indicate that the distribution pattern of SVs among the 3D genome is highly cell-type specific and the bulk remodeling effects of SVs in the chromatin organization partly depend on intercellular genomic heterogeneity. Meanwhile, contact domains tend to minimize these disrupting effects of SVs within local adjacent genomic regions to maintain overall stability. Notably, complex genomic rearrangements involving two key driver genes CDKN2A and SMAD4 are identified, and their influence on the expression of oncogenes MIR31HG, MYO5B, etc., are further elucidated from both a linear view and 3D perspective. Overall, this work provides a genome-wide resource and highlights the impact, complexity, and dynamicity of the interplay between structural variations and high-order chromatin organization, which expands the current understanding of the pathogenesis of SVs in human cancer.

show abstract

Juicer Provides a One-Click System for Analyzing Loop-Resolution Hi-C Experiments

Cited by 2,228 publications

References 9 publications

Long-range chromatin interactions on the inactive X and atHoxclusters are regulated by the non-canonical SMC protein Smchd1

Long-range chromatin interactions on the inactive X and atHoxclusters are regulated by the non-canonical SMC protein Smchd1

Circular Trajectory Reconstruction Uncovers Cell‐Cycle Progression and Regulatory Dynamics from Single‐Cell Hi‐C Maps

Dynamic Interplay between Structural Variations and 3D Genome Organization in Pancreatic Cancer

Contact Info

Product

Resources

About