Article
Biochemistry & Molecular Biology
Kyukwang Kim, Inkyung Jung
Summary: The development of the covNorm method for Hi-C and its variants shows enhanced reproducibility and effectiveness in normalizing data, detecting long-range chromatin contacts, and extending to other derivative Hi-C protocols.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemical Research Methods
Han Li, Xuan He, Lawrence Kurowski, Ruotian Zhang, Dan Zhao, Jianyang Zeng
Summary: Hi-C is a widely used technique for studying the relationships between biological functionalities and the three-dimensional genome structure. However, conducting comparative analyses of Hi-C data is challenging due to the complex nature of Hi-C contact maps. In this study, we proposed a contrastive self-supervised representation learning framework, sslHiC, which accurately models the multi-level features of chromosome conformation and automatically produces informative feature embeddings for comparative analyses of Hi-C contact maps.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Chemistry, Multidisciplinary
Junmei Wang, Lu Lu, Shiqi Zheng, Danyang Wang, Long Jin, Qing Zhang, Mingzhou Li, Zhihua Zhang
Summary: Deciphering variations in chromosome conformations is crucial for understanding cell-type specific genome architecture and dynamics. This study developed a deep convolutional neural network called deCOOC, which outperformed all the state-of-the-art tools in the deconvolution task of high-throughput chromosome conformation capture (Hi-C) data. It was found that the chromatin accessibility or Hi-C contact frequency alone is insufficient to explain the power of deCOOC, suggesting the existence of a latent embedded layer of information pertaining to the cell type specific 3D genome architecture. Applying deCOOC to bulk Hi-C data from different adipose tissues revealed distinct chromatin features associated with different physiological functionalities of M2 cells. Overall, deCOOC is a reliable method for Hi-C data deconvolution and functional extraction of 3D genome architecture.
Article
Multidisciplinary Sciences
Yanping Liu, Yufei Wang, Lu Yang, Feng Sun, Sheng Li, Yequan Wang, Guo-An Zhang, Tingting Dong, Lei-Lei Zhang, Wanglin Duan, Xiaojun Zhang, Wen Cui, Su Chen
Summary: Histone H2B is mainly degraded through the proteasome-mediated pathway, with the lysine-120 site of H2B essential for its degradation. The nucleolus may play a role in H2B degradation, providing a novel mechanism for the regulation of H2B degradation.
Article
Biochemical Research Methods
Victoria A. Kobets, Sergey Ulianov, Aleksandra A. Galitsyna, Semen A. Doronin, Elena A. Mikhaleva, Mikhail S. Gelfand, Yuri Y. Shevelyov, Sergey Razin, Ekaterina E. Khrameeva
Summary: The study introduces a novel approach called HiConfidence, which effectively eliminates technical biases from Hi-C data for more accurate analysis of genome structure changes and meaningful biological conclusions.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Cheynna Crowley, Yuchen Yang, Yunjiang Qiu, Benxia Hu, Armen Abnousi, Jakub Lipinski, Dariusz Plewczynski, Di Wu, Hyejung Won, Bing Ren, Ming Hu, Yun Li
Summary: The FIREcaller package is a user-friendly R tool developed for detecting FIREs from Hi-C data, which has been demonstrated to be closely related to gene regulation in a tissue-specific manner and enriched for enhancer-promoter interactions.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemical Research Methods
Huiling Liu, Wenxiu Ma
Summary: In this study, we introduced the scHiCDiff software tool that can detect differential chromatin interactions (DCIs) from single-cell Hi-C data using both nonparametric tests and parametric models. We thoroughly evaluated the scHiCDiff methods on simulated and real data, and our results demonstrated that scHiCDiff, especially the zero-inflated negative binomial model option, can effectively detect reliable and consistent single-cell DCIs between two conditions, thereby facilitating the study of cell type-specific variations of chromatin structures at the single-cell level.
Article
Biology
Mikhail G. Dozmorov, Katarzyna M. Tyc, Nathan C. Sheffield, David C. Boyd, Amy L. Olex, Jason Reed, J. Chuck Harrell
Summary: The removal of mouse reads had minimal impact on data quality in Hi-C analysis, with Juicer showing superior performance in extracting valid chromatin interactions. The choice of pipeline had minimal effect on results, while library preparation strategy had the largest impact on quality metrics. This study provides comprehensive guidelines for processing PDX Hi-C data.
Article
Multidisciplinary Sciences
Abhijit Chakraborty, Jeffrey G. Wang, Ferhat Ay
Summary: In this study, a method called dcHiC is introduced, which uses a multivariate distance measure to identify significant changes in compartmentalization among multiple contact maps. The effectiveness and sensitivity of dcHiC in detecting biologically relevant changes are demonstrated through evaluations on different datasets. dcHiC enables high-resolution compartment analysis and provides additional features such as browser visualization, differential interaction identification, and time-series clustering.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Dina Aljogol, I. Richard Thompson, Cameron S. Osborne, Borbala Mifsud
Summary: This article discusses multiple computational pipelines for CHi-C data analysis and compares their efficiency in identifying reproducible interactions and determining biologically significant interactions. The study finds that the optimal pipeline depends on the project-specific tolerance level for false positives and false negatives in chromatin contacts.
FRONTIERS IN GENETICS
(2022)
Review
Cell Biology
Kyukwang Kim, Mooyoung Kim, Yubin Kim, Dongsung Lee, Inkyung Jung
Summary: Hi-C technology plays a crucial role in genome analysis, particularly in the detection of large-scale structural variations. Recent studies have also explored the potential of Hi-C at the single-cell level for investigating genomic rearrangements.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemical Research Methods
Aleksandra A. Galitsyna, Mikhail S. Gelfand
Summary: Genome-wide assays for chromatin interactions in single cells have advanced in the past decade, but specialized processing is still needed for sparse interactome data recovery. These methods have highlighted directions for future development in this rapidly moving field.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Plant Sciences
Jin Han, Siyuan Wang, Hongyu Wu, Ting Zhao, Xueying Guan, Lei Fang
Summary: Researchers improved the Hi-C technology for plants by optimizing cross-linking agents and endonuclease fragmentation strategy, and designed a systematic in situ Hi-C protocol to monitor library construction quality. This upgraded method, called Hi-C 3.0, was tested on cotton leaves and showed improved signal-to-noise ratio, higher capturing of loops, and more accurate compartment detection compared to the conventional Hi-C 2.0. Overall, Hi-C 3.0 advances the Hi-C method in plants and enhances the decoding of chromatin organization.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Immunology
Yu Xia, Xiaowen Liu, Wenli Mu, Chunyan Ma, Laicheng Wang, Yulian Jiao, Bin Cui, Shengnan Hu, Ying Gao, Tao Liu, Huanxin Sun, Shuai Zong, Xin Liu, Yueran Zhao
Summary: This study investigates the chromatin regulation and heterogeneity in human primary monocytes using Hi-C, RNA-seq, ATAC-seq, and ChIP-seq analyses. The results reveal the stability and variability of high-resolution chromatin interaction maps in human primary monocytes, as well as the notable variability around the HLA complex region. Furthermore, the study suggests that chromatin loop dynamics may modulate CD16 expression.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiaoqi Li, Lindsay Lee, Armen Abnousi, Miao Yu, Weifang Liu, Le Huang, Yun Li, Ming Hu
Summary: Single cell Hi-C technologies enable the study of chromatin spatial organization directly from complex tissues at single cell resolution. SnapHiC2 provides an efficient tool to identify chromatin loops from scHi-C data by using a sliding window approximation and reducing computational resources. It can accurately identify chromatin loops and suggest target genes for GWAS variants in a cell-type-specific manner.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Cell Biology
Susanne Leidescher, Johannes Ribisel, Simon Ullrich, Yana Feodorova, Erica Hildebrand, Alexandra Galitsyna, Sebastian Bultmann, Stephanie Link, Katharina Thanisch, Christopher Mulholland, Job Dekker, Heinrich Leonhardt, Leonid Mirny, Irina Solovei
Summary: Despite limited understanding of the spatial organization of the genome, this study demonstrates that highly expressed long genes form open-ended transcription loops with RNA polymerases moving along them. The extension and shape of these loops suggest intrinsic stiffness and could represent a general mechanism underlying eukaryotic transcription.
NATURE CELL BIOLOGY
(2022)
Article
Biology
Guoxin Cui, Yi Jin Liew, Migle K. Konciute, Ye Zhan, Shiou-Han Hung, Jana Thistle, Lucia Gastoldi, Sebastian Schmidt-Roach, Job Dekker, Manuel Aranda
Summary: This study investigates the effects of nitrogen limitation on symbiont cell proliferation and life stage transitions in coral-algal symbiosis, and identifies nitrogen availability as a major factor limiting symbiont density and life stage transitions.
Article
Evolutionary Biology
Lewis Stevens, Nicolas D. Moya, Robyn E. Tanny, Sophia B. Gibson, Alan Tracey, Huimin Na, Rojin Chitrakar, Job Dekker, Albertha J. M. Walhout, L. Ryan Baugh, Erik C. Andersen
Summary: This study constructed chromosome-level reference genomes for two strains of Caenorhabditis briggsae using high-coverage sequencing data. The comparison with the reference genome of C. elegans revealed substantial differences, including the presence of hyper-divergent haplotypes in the C. briggsae genome. The study also showed that selfing Caenorhabditis species have undergone more rearrangement, biasing previous estimates of rearrangement rate.
GENOME BIOLOGY AND EVOLUTION
(2022)
Article
Biochemistry & Molecular Biology
Stefanos K. Nomidis, Enrico Carlon, Stephan Gruber, John F. Marko
Summary: Structural Maintenance of Chromosomes (SMC) complexes play critical roles in genome organization. Researchers developed a molecular dynamics model to investigate the control of SMC complex activities by ATP binding and hydrolysis. The model revealed the sensitivity of this process to DNA tension and the ability of the SMC complex to perform loop extrusion by tethering DNA to an additional binding site.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Jacob T. Sanders, Rosela Golloshi, Priyojit Das, Yang Xu, Peyton H. Terry, Darrian G. Nash, Job Dekker, Rachel Patton McCord
Summary: This study investigates the effects of chromatin extension during volume changes using low-salt swelling and genome-wide chromosome conformation capture technology. The results show that global genome structure remains stable despite significant nuclear volume swelling. Extension of the local chromatin fiber leads to changes in contact probabilities, but loops, TADs, active and inactive compartments, and chromosome territories are maintained. This suggests that genome topology is robust to chromatin fiber extension and shape changes.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Daniel J. Emerson, Peiyao A. Zhao, Ashley L. Cook, R. Jordan Barnett, Kyle N. Klein, Dalila Saulebekova, Chunmin Ge, Linda Zhou, Zoltan Simandi, Miriam K. Minsk, Katelyn R. Titus, Weitao Wang, Wanfeng Gong, Di Zhang, Liyan Yang, Sergey V. Venev, Johan H. Gibcus, Hongbo Yang, Takayo Sasaki, Masato T. Kanemaki, Feng Yue, Job Dekker, Chun-Long Chen, David M. Gilbert, Jennifer E. Phillips-Cremins
Summary: This article reveals the determinants of replication origin positioning in the human genome. The study found that topologically associating domains and loops play crucial roles in the localization of replication initiation zones. By disrupting cohesin-mediated loop extrusion, the positioning of replication origins can be altered. These findings contribute to a better understanding of the mechanism of DNA replication.
Review
Biochemistry & Molecular Biology
Bastiaan Dekker, Job Dekker
Summary: Significant progress has been made in identifying the molecular machines involved in chromosome folding, such as condensins and topoisomerases, in recent years. The discovery of condensins generating chromatin loops through loop extrusion has greatly impacted and energized the field. Current understanding suggests that these machines and factors are regulated through cell cycle dependent expression, chromatin localization, post-translational modifications, and associations with other factors and the chromatin template. Although there are still unanswered questions about the regulation of condensins and topoisomerases, it is likely that many of these will be addressed in the future, given the pace of progress in the field of chromosome folding.
BIOCHEMICAL JOURNAL
(2022)
Article
Cell Biology
Yu Liu, Job Dekker
Summary: The cohesin complex plays a crucial role in sister-chromatid cohesion and chromatin looping, but its mechanisms vary depending on the genomic context.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jennifer Zagelbaum, Allana Schooley, Junfei Zhao, Benjamin R. Schrank, Elsa Callen, Shan Zha, Max E. Gottesman, Andre Nussenzweig, Raul Rabadan, Job Dekker, Jean Gautier
Summary: Research shows that nuclear actin movements are involved in clustering DNA double-strand breaks (DSBs) for homology-directed repair. This study explores the three-dimensional reorganization of the genome after DNA damage and examines the role of the nuclear WASP-ARP2/3-actin pathway in chromatin topology changes during pathological repair. The results indicate that DNA damage induces genome-wide chromatin compartment flips mediated by ARP2/3, leading to enrichment of open, A compartments. Additionally, DSB interactions promote aberrant actin-dependent rearrangements within and between chromosomes. This work demonstrates that nuclear actin assembly orchestrates DSB clustering for repair while also impacting genome architecture and translocation frequency.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anne-Laure Valton, Sergey V. Venev, Barbara Mair, Eraj Shafiq Khokhar, Amy H. Y. Tong, Matej Usaj, Katherine Chan, Athma A. Pai, Jason Moffat, Job Dekker
Summary: Cohesin-mediated loop extrusion is blocked at specific cis-elements, resulting in patterns of loops and domain boundaries along chromosomes. Transcription termination sites of active genes form cohesin-dependent boundaries without accumulating cohesin, while start sites of transcriptionally active genes form cohesin-bound boundaries. Disrupting the traffic pattern of cohesin by removing CTCF renders cells sensitive to knockout of genes involved in transcription initiation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
George Spracklin, Nezar Abdennur, Maxim Imakaev, Neil Chowdhury, Sriharsa Pradhan, Leonid A. A. Mirny, Job Dekker
Summary: In this study, the researchers profiled long-range contact frequencies in HCT116 colon cancer cells and identified three silent chromatin states. They found that heterochromatin marked by H3K9me3, HP1 alpha, and HP1 beta showed strong compartmentalization. Their findings also showed that disruption of DNA methyltransferase activity altered genome compartmentalization, leading to changes in chromatin state and chromosome organization.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Correction
Biochemistry & Molecular Biology
Jennifer Zagelbaum, Allana Schooley, Junfei Zhao, Benjamin R. Schrank, Elsa Callen, Shan Zha, Max E. Gottesman, Andre Nussenzweig, Raul Rabadan, Job Dekker, Jean Gautier
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biology
Coral Y. Zhou, Bastiaan Dekker, Ziyuan Liu, Hilda Cabrera, Joel Ryan, Job Dekker, Rebecca Heald
Summary: This study reveals that the size of mitotic chromosomes is controlled by spatially and temporally distinct developmental cues. The scaling of mitotic chromosomes involves mechanisms different from other subcellular structures such as spindles and nuclei. It is regulated by factors such as cell, spindle and nuclear size, as well as the nuclear-cytoplasmic ratio and importin alpha. Additionally, the shrinking of mitotic chromosomes during embryogenesis is attributed to decreased recruitment of condensin I and rearrangement of DNA loop architecture.
Article
Biochemistry & Molecular Biology
Job Dekker, Frank Alber, Sarah Aufmkolk, Brian J. Beliveau, Benoit G. Bruneau, Andrew S. Belmont, Lacramioara Bintu, Alistair Boettiger, Riccardo Calandrelli, Christine M. Disteche, David M. Gilbert, Thomas Gregor, Anders S. Hansen, Bo Huang, Danwei Huangfu, Reza Kalhor, Christina S. Leslie, Wenbo Li, Yun Li, Jian Ma, William S. Noble, Peter J. Park, Jennifer E. Phillips-Cremins, Katherine S. Pollard, Susanne M. Rafelski, Bing Ren, Yijun Ruan, Yaron Shav-Tal, Yin Shen, Jay Shendure, Xiaokun Shu, Caterina Strambio-De-Castillia, Anastassiia Vertii, Huaiying Zhang, Sheng Zhong
Summary: The four-dimensional nucleome (4DN) consortium investigates the structure and temporal-spatial characteristics of the genome and nucleus. The consortium has made significant progress in mapping genome folding, identifying nuclear components and bodies, and imaging nuclear organization. The generated datasets have been used to develop computational models that reveal connections between genome structure and function. Future aims include studying dynamics of nuclear architecture, understanding cis-determinants and trans-modulators of genome organization, exploring functional consequences of changes in regulators, and developing predictive models
