Method to Watch |
Featured
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Research Briefing |
Multifactorial epigenomic profiling of six chromatin states in single cells
We developed MAbID, a method for combined genomic profiling of histone modifications and chromatin-binding proteins in single cells, enabling researchers to study the interconnectivity between gene-regulatory mechanisms. We demonstrated MAbID’s implementation in profiling multifactorial changes in chromatin signatures during in vitro neural differentiation and in primary mouse bone marrow tissue.
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Research Highlight |
A closer look at chromatin
An expansion microscopy technique called ChromExM offers detailed views into the organization chromatin and associated gene expression machinery in embryos.
- Rita Strack
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Research Briefing |
Genome architecture mapping detects transcriptionally active, multiway chromatin contacts
Genome architecture mapping (GAM) enables understanding of 3D genome structure in the nucleus. We directly compared multiplex-GAM and Hi-C data and found that local chromatin interactions were generally detected by both methods, but active genomic regions rich in enhancers that established higher-order contacts were preferentially detected by GAM.
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Article
| Open AccessMultiplex-GAM: genome-wide identification of chromatin contacts yields insights overlooked by Hi-C
Multiplex-genome architecture mapping (multiplex-GAM) enables rapid, unbiased, ligation-free mapping of genome-wide chromatin interactions.
- Robert A. Beagrie
- , Christoph J. Thieme
- & Ana Pombo
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News & Views |
Mapping beads on strings
DiMeLo-seq leverages immunotethered DNA methyltransferases with long-read sequencing to map the locations of chromatin proteins in their natural context.
- Kami Ahmad
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Article |
DiMeLo-seq: a long-read, single-molecule method for mapping protein–DNA interactions genome wide
DiMeLo-seq uses native long-read sequencing to examine protein–DNA interactions by mapping exogenous methylation marks generated by a nonspecific DNA methyltransferase, as well as profile endogenous CpG methylation simultaneously.
- Nicolas Altemose
- , Annie Maslan
- & Aaron Streets
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Method to Watch |
Greater detail in the nucleus
Probing spatially organized DNA and its interacting elements in single cells will deepen our understanding of cell-type-specific gene regulation.
- Lei Tang
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Research Highlight |
Mapping genome structures in single cells
Researchers develop single-cell SPRITE to detect higher-order 3D genome structures in single cells.
- Lei Tang
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Brief Communication
| Open AccessSnapHiC: a computational pipeline to identify chromatin loops from single-cell Hi-C data
SnapHiC offers a computational tool for improving detection of chromatin loops from single-cell Hi-C data.
- Miao Yu
- , Armen Abnousi
- & Ming Hu
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Article |
Single-cell joint detection of chromatin occupancy and transcriptome enables higher-dimensional epigenomic reconstructions
This paper reports CoTECH, which couples chromatin binding enrichment with RNA sequencing for concurrent measurements of histone modification and transcriptome in single cells, offering a multiomics tool for studying epigenetic regulations.
- Haiqing Xiong
- , Yingjie Luo
- & Aibin He
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Research Highlight |
Sequencing DNA bendability
Loop-seq is a high-throughput sequencing assay that measures DNA looping and can help explain how DNA bendability contributes to nucleosome organization.
- Lei Tang
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Article |
DeepC: predicting 3D genome folding using megabase-scale transfer learning
DeepC uses transfer learning-based deep neural networks for predicting genome folding from megabase-scale DNA sequence.
- Ron Schwessinger
- , Matthew Gosden
- & Jim R. Hughes
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Article |
Predicting 3D genome folding from DNA sequence with Akita
Akita enables three-dimensional genome folding predictions from DNA sequence using a convolutional neural network.
- Geoff Fudenberg
- , David R. Kelley
- & Katherine S. Pollard
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Article |
3D mapping and accelerated super-resolution imaging of the human genome using in situ sequencing
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.
- Huy Q. Nguyen
- , Shyamtanu Chattoraj
- & C.-ting Wu
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Research Highlight |
Radial genome organization
Sequencing gradually digested chromatin along the nuclear radius enables the mapping of radial organization of chromatin in human cells.
- Lei Tang
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Perspective |
Mechanistic modeling of chromatin folding to understand function
This Perspective highlights recently developed computational models for studying chromosome organization, with a focus on how mechanistic modeling helps biologists to interpret the biological function behind the genome structures.
- Chris A. Brackey
- , Davide Marenduzzo
- & Nick Gilbert
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Research Highlight |
Identifying the chromatin-associated proteome
ChromID identifies proteins associated with various chromatin modifications.
- Arunima Singh
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Perspective |
Purification and enrichment of specific chromatin loci
This Perspective discusses the challenges, progress and future of proteome profiling at specific chromatin loci for elucidating genome biology.
- Mathilde Gauchier
- , Guido van Mierlo
- & Jérôme Déjardin
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Article |
Simultaneous profiling of 3D genome structure and DNA methylation in single human cells
Single-nucleus methyl-3C sequencing jointly interrogates 3D chromatin organization and DNA methylation in human cells, and these joint measurements more accurately distinguish different cell types than either unimodal method.
- Dong-Sung Lee
- , Chongyuan Luo
- & Joseph R. Ecker
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Brief Communication |
HiChIRP reveals RNA-associated chromosome conformation
HiChIRP combines a modified chromosome conformation capture protocol with enrichment of RNA-associated chromosome conformation to visualize genome-wide looping linked to an RNA of interest.
- Maxwell R. Mumbach
- , Jeffrey M. Granja
- & Howard Y. Chang
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Research Highlight |
Variability in genome structure
Comparisons of genome organization in many individual cells with high-throughput FISH show extensive variation.
- Nicole Rusk
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Research Highlight |
Diploid genome in 3D
Dip-C, a descendent of the 3C method, reveals 3D genome structures of single diploid human cells.
- Lei Tang
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Article |
Trac-looping measures genome structure and chromatin accessibility
Insertion of a bivalent linker between two regions of interest allows chromatin contacts to be probed without proximity ligation.
- Binbin Lai
- , Qingsong Tang
- & Keji Zhao
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Research Highlight |
Polymer model predicts chromatin folding
3C-based methods and polymer modeling indentify the impact of structural variants.
- Lei Tang
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Brief Communication |
Discovery of proteins associated with a predefined genomic locus via dCas9–APEX-mediated proximity labeling
After CRISPR-mediated targeting of the peroxidase APEX2 to a genomic locus of interest, the proteins at that locus are labeled, enriched and identified via quantitative proteomics.
- Samuel A. Myers
- , Jason Wright
- & Steven A. Carr
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Brief Communication |
C-BERST: defining subnuclear proteomic landscapes at genomic elements with dCas9–APEX2
dCas9 fused to ascorbate peroxidase (APEX2) biotinylates proteins around targeted loci so they can be enriched and characterized.
- Xin D. Gao
- , Li-Chun Tu
- & Erik J. Sontheimer
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Research Highlights |
Humanized yeast—erasing 1.3 billion years of evolution
Cellular engineering that allows budding yeast to survive with the four core human histones opens the door to exploring the function of histone variants and their modifications.
- Nicole Rusk
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Research Highlights |
Seeing DNA
DNA and chromatin structures can be visualized in situ with electron tomography.
- Zachary J Lapin
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Research Highlights |
What comes first—genomic structure or function?
CRISPR-mediated chromatin looping provides insight into the effect of genomic structure on gene expression.
- Nicole Rusk
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Research Highlights |
Native chromosome conformation
Isolation of nuclei in an isotonic buffer retains chromosome loops and allows the probing of intrinsic loop conformation.
- Nicole Rusk
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Research Highlights |
A pluripotent approach
A combination of protein and DNA isolation methods expands our grasp of cellular reprogramming.
- Stéphane Larochelle
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Research Highlights |
Learning the histone language
Sequential rounds of immunoprecipitation and barcoding reveal the genome-wide occurrence of paired histone marks.
- Nicole Rusk
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Technology Feature |
Genomics in 3D and 4D
DNA folding shapes gene expression. Emerging techniques promise to reveal the intricacies of this architectural language of chromosomes.
- Vivien Marx
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Methods in Brief |
Imaging chromosome organization
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Article |
UMI-4C for quantitative and targeted chromosomal contact profiling
UMI-4C is a rapid, simplified barcoding approach to targeted chromatin conformation capture that produces high-complexity libraries from low sample input, is easily multiplexed and gives a quantitative, statistically defined readout.
- Omer Schwartzman
- , Zohar Mukamel
- & Amos Tanay
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Research Highlights |
Retraining an editor as a mapmaker
A sequence-specific labeling system based on CRISPR/Cas9 enables simultaneous imaging of multiple chromosomal sites in live cells.
- Michael Eisenstein
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Research Highlights |
Light-responsive enzyme inhibitors
A hybrid of a photo-responsive ligand and a small-molecule inhibitor enables optical control of epigenetic mechanisms.
- Nicole Rusk
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Perspective |
Genome-wide footprinting: ready for prime time?
The Perspective by Sung, Baek and Hager discusses consensus, remaining issues and hurdles for genomic footprinting.
- Myong-Hee Sung
- , Songjoon Baek
- & Gordon L Hager
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Perspective |
Genomic footprinting
This Perspective by Vierstra and Stamatoyannopoulos discusses the prospects and challenges of genomic footprinting applied to complex genomes.
- Jeff Vierstra
- & John A Stamatoyannopoulos
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Analysis |
Analysis of computational footprinting methods for DNase sequencing experiments
This comparison of ten computational methods for detecting transcription factor binding sites in DNase hypersensitive regions in the genome determines which methods work consistently well, how DNase-seq experimental artifacts should be corrected for and which score is best for ranking methods.
- Eduardo G Gusmao
- , Manuel Allhoff
- & Ivan G Costa
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Methods in Brief |
Capturing lysine PTM–dependent interactions
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This Month |
Jason W. Chin
How to combine biology, chemistry and synthetic biology to add synthetic amino acids to a protein, and why creativity matters.
- Vivien Marx
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Article |
Genetic code expansion in stable cell lines enables encoded chromatin modification
Stable integration of genes that facilitate the incorporation of unnatural amino acids into the amber stop codon in genes of interest allows targeted integration of acetyl-lysine into histone H3.3 and the investigation of its effects in mouse embryonic stem cells.
- Simon J Elsässer
- , Russell J Ernst
- & Jason W Chin
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Method to Watch |
Unraveling nuclear architecture
New approaches are needed to see the dynamics of 3D chromatin structure at high resolution and throughput.
- Nicole Rusk
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Research Highlights |
A single cell's open chromatin
Increasing the sensitivity of DNase-seq allows chromatin accessibility to be profiled from very low numbers of cells.
- Nicole Rusk
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Brief Communication |
ChIPmentation: fast, robust, low-input ChIP-seq for histones and transcription factors
ChIPmentation combines chromatin immunoprecipitation with on-bead tagmentation for rapid and highly robust ChIP-seq library preparation.
- Christian Schmidl
- , André F Rendeiro
- & Christoph Bock