scholarly journals ARID1A spatially partitions interphase chromosomes

2019 ◽  
Vol 5 (5) ◽  
pp. eaaw5294 ◽  
Author(s):  
Shuai Wu ◽  
Nail Fatkhutdinov ◽  
Leah Rosin ◽  
Jennifer M. Luppino ◽  
Osamu Iwasaki ◽  
...  
Keyword(s):  
Genome Organization ◽  
Large Scale ◽  
Three Dimensional ◽  
Higher Order ◽  
Interphase Chromosome ◽  
Chromatin Remodeling Complex ◽  
Chromosome Partitioning ◽  
Topologically Associated Domains ◽  
A Subunit

ARID1A, a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex, localizes to both promoters and enhancers to influence transcription. However, the role of ARID1A in higher-order spatial chromosome partitioning and genome organization is unknown. Here, we show that ARID1A spatially partitions interphase chromosomes and regulates higher-order genome organization. The SWI/SNF complex interacts with condensin II, and they display significant colocalizations at enhancers. ARID1A knockout drives the redistribution of condensin II preferentially at enhancers, which positively correlates with changes in transcription. ARID1A and condensin II contribute to transcriptionally inactive B-compartment formation, while ARID1A weakens the border strength of topologically associated domains. Condensin II redistribution induced by ARID1A knockout positively correlates with chromosome sizes, which negatively correlates with interchromosomal interactions. ARID1A loss increases the trans interactions of small chromosomes, which was validated by three-dimensional interphase chromosome painting. These results demonstrate that ARID1A is important for large-scale genome folding and spatially partitions interphase chromosomes.

scholarly journals Deciphering the Role of 3D Genome Organization in Breast Cancer Susceptibility

2022 ◽  
Vol 12 ◽  
Author(s):  
Brittany Baur ◽  
Da-Inn Lee ◽  
Jill Haag ◽  
Deborah Chasman ◽  
Michael Gould ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genome Organization ◽  
Mammary Epithelial Cells ◽  
Cancer Susceptibility ◽  
Three Dimensional ◽  
Breast Cancer Susceptibility ◽  
Higher Order ◽  
Mammary Epithelial ◽  
3D Genome

Cancer risk by environmental exposure is modulated by an individual’s genetics and age at exposure. This age-specific period of susceptibility is referred to as the “Window of Susceptibility” (WOS). Rats have a similar WOS for developing breast cancer. A previous study in rat identified an age-specific long-range regulatory interaction for the cancer gene, Pappa, that is associated with breast cancer susceptibility. However, the global role of three-dimensional genome organization and downstream gene expression programs in the WOS is not known. Therefore, we generated Hi-C and RNA-seq data in rat mammary epithelial cells within and outside the WOS. To systematically identify higher-order changes in 3D genome organization, we developed NE-MVNMF that combines network enhancement followed by multitask non-negative matrix factorization. We examined three-dimensional genome organization dynamics at the level of individual loops as well as higher-order domains. Differential chromatin interactions tend to be associated with differentially up-regulated genes with the WOS and recapitulate several human SNP-gene interactions associated with breast cancer susceptibility. Our approach identified genomic blocks of regions with greater overall differences in contact count between the two time points when the cluster assignments change and identified genes and pathways implicated in early carcinogenesis and cancer treatment. Our results suggest that WOS-specific changes in 3D genome organization are linked to transcriptional changes that may influence susceptibility to breast cancer.

scholarly journals Erythrocytes 3D genome organization in vertebrates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anastasia Ryzhkova ◽  
Alena Taskina ◽  
Anna Khabarova ◽  
Veniamin Fishman ◽  
Nariman Battulin
Keyword(s):  
Blood Cells ◽  
Genome Organization ◽  
Large Scale ◽  
Chromatin Condensation ◽  
Erythroid Differentiation ◽  
Interaction Patterns ◽  
3D Interaction ◽  
Interphase Chromosome ◽  
3D Genome ◽  
Contact Maps

AbstractGeneration of mature red blood cells, consisting mainly of hemoglobin, is a remarkable example of coordinated action of various signaling networks. Chromatin condensation is an essential step for terminal erythroid differentiation and subsequent nuclear expulsion in mammals. Here, we profiled 3D genome organization in the blood cells from ten species belonging to different vertebrate classes. Our analysis of contact maps revealed a striking absence of such 3D interaction patterns as loops or TADs in blood cells of all analyzed representatives. We also detect large-scale chromatin rearrangements in blood cells from mammals, birds, reptiles and amphibians: their contact maps display strong second diagonal pattern, representing an increased frequency of long-range contacts, unrelated to TADs or compartments. This pattern is completely atypical for interphase chromosome structure. We confirm that these principles of genome organization are conservative in vertebrate erythroid cells.

scholarly journals Genome organization via loop extrusion, insights from polymer physics models

2019 ◽  
Vol 19 (2) ◽  
pp. 119-127 ◽  
Author(s):  
Surya K Ghosh ◽  
Daniel Jost
Keyword(s):  
Genome Organization ◽  
Extrusion Process ◽  
Polymer Physics ◽  
Modern Biology ◽  
Precise Information ◽  
Multi Scale ◽  
Topologically Associated Domains ◽  
Structural Maintenance Of Chromosome ◽  
Smc Proteins

Abstract Understanding how genomes fold and organize is one of the main challenges in modern biology. Recent high-throughput techniques like Hi-C, in combination with cutting-edge polymer physics models, have provided access to precise information on 3D chromosome folding to decipher the mechanisms driving such multi-scale organization. In particular, structural maintenance of chromosome (SMC) proteins play an important role in the local structuration of chromatin, putatively via a loop extrusion process. Here, we review the different polymer physics models that investigate the role of SMCs in the formation of topologically associated domains (TADs) during interphase via the formation of dynamic loops. We describe the main physical ingredients, compare them and discuss their relevance against experimental observations.

Low Temperature Cu–Cu Bonding Technology in Three-Dimensional Integration: An Extensive Review

2018 ◽  
Vol 140 (1) ◽  
Author(s):  
Asisa Kumar Panigrahy ◽  
Kuan-Neng Chen
Keyword(s):  
Low Temperature ◽  
Integrated Circuit ◽  
Large Scale ◽  
Three Dimensional ◽  
3D Ic ◽  
Bonding Technology ◽  
Three Dimensional Integrated Circuit ◽  
Low Temperature Bonding ◽  
Cu Bonding

Arguably, the integrated circuit (IC) industry has received robust scientific and technological attention due to the ultra-small and extremely fast transistors since past four decades that consents to Moore's law. The introduction of new interconnect materials as well as innovative architectures has aided for large-scale miniaturization of devices, but their contributions were limited. Thus, the focus has shifted toward the development of new integration approaches that reduce the interconnect delays which has been achieved successfully by three-dimensional integrated circuit (3D IC). At this juncture, semiconductor industries utilize Cu–Cu bonding as a key technique for 3D IC integration. This review paper focuses on the key role of low temperature Cu–Cu bonding, renaissance of the low temperature bonding, and current research trends to achieve low temperature Cu–Cu bonding for 3D IC and heterogeneous integration applications.

scholarly journals Acute condensin depletion causes genome decompaction without altering the level of global gene expression in Saccharomyces cerevisiae

2017 ◽  
Author(s):  
Matthew Robert Paul ◽  
Tovah Elise Markowitz ◽  
Andreas Hochwagen ◽  
Sevinç Ercan
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Genome Organization ◽  
Large Scale ◽  
Global Gene Expression ◽  
Higher Order ◽  
Gene Clustering ◽  
Global Changes ◽  
Chromatin Compaction ◽  
And Function

AbstractCondensins are broadly conserved chromosome organizers that function in chromatin compaction and transcriptional regulation, but to what extent these two functions are linked has remained unclear. Here, we analyzed the effect of condensin inactivation on genome compaction and global gene expression in the yeast Saccharomyces cerevisiae. Spike-in-controlled 3C-seq analysis revealed that acute condensin inactivation leads to a global decrease in close-range chromosomal interactions as well as more specific losses of homotypic tRNA gene clustering. In addition, a condensin-rich topologically associated domain between the ribosomal DNA and the centromere on chromosome XII is lost upon condensin inactivation. Unexpectedly, these large-scale changes in chromosome architecture are not associated with global changes in transcript levels as determined by spike-in-controlled mRNA-seq analysis. Our data suggest that the global transcriptional program of S. cerevisiae is resistant to condensin inactivation and the associated profound changes in genome organization.Significance StatementGene expression occurs in the context of higher-order chromatin organization, which helps compact the genome within the spatial constraints of the nucleus. To what extent higher-order chromatin compaction affects gene expression remains unknown. Here, we show that gene expression and genome compaction can be uncoupled in the single-celled model eukaryote Saccharomyces cerevisiae. Inactivation of the conserved condensin complex, which also organizes the human genome, leads to broad genome decompaction in this organism. Unexpectedly, this reorganization has no immediate effect on the transcriptome. These findings indicate that the global gene expression program is robust to large-scale changes in genome architecture in yeast, shedding important new light on the evolution and function of genome organization in gene regulation.

scholarly journals Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

2020 ◽  
Author(s):  
Lei Chang ◽  
Mengfan Li ◽  
Shipeng Shao ◽  
Chen Li ◽  
Shanshan Ai ◽  
...  
Keyword(s):  
Nuclear Periphery ◽  
Three Dimensional ◽  
Higher Order ◽  
Order Structure ◽  
Chromatin Dynamics ◽  
Lamin B1 ◽  
Chromatin Architecture ◽  
Chromatin Interactions ◽  
Molecular Machinery

Abstract The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.

scholarly journals Identification of decondensed large-scale chromatin regions by TSA-seq and their localization to a subset of chromatin domain boundaries

2021 ◽  
Author(s):  
Omid Gholamalamdari ◽  
Liguo Zhang ◽  
Yu Chen ◽  
Andrew Belmont
Keyword(s):  
Genome Organization ◽  
Large Scale ◽  
Chromatin Domain ◽  
Interphase Chromosome ◽  
Chromatin Domains ◽  
Nuclear Compartment ◽  
Chromatin Compaction ◽  
Domain Boundaries ◽  
Chromatin Remodeling Complexes ◽  
Local Enrichment

AbstractLarge-scale chromatin compaction is nonuniform across the human genome and correlates with gene expression and genome organization. Current methodologies for assessing large-scale chromatin compaction are indirect and largely based on assays that probe lower levels of chromatin organization, primarily at the level of the nucleosome and/or the local compaction of nearby nucleosomes. These assays assume a one-to-one correlation between local nucleosomal compaction and large-scale compaction of chromosomes that may not exist. Here we describe a method to identify interphase chromosome regions with relatively high levels of large-scale chromatin decondensation using TSA-seq, which produces a signal proportional to microscopic-scale distances relative to a defined nuclear compartment. TSA-seq scores that change rapidly as a function of genomic distance, detected by their higher slope values, identify decondensed large-scale chromatin domains (DLCDs), as then validated by 3D DNA-FISH. DLCDs map near a subset of chromatin domain boundaries, defined by Hi-C, which separate active and repressed chromatin domains and correspond to compartment, subcompartment, and some TAD boundaries. Most DLCDs can also be detected by high slopes of their Hi-C compartment score. In addition to local enrichment in cohesin (RAD21, SMC3) and CTCF, DLCDs show the highest local enrichment to super-enhancers, but are also locally enriched in transcription factors, histone-modifying complexes, chromatin mark readers, and chromatin remodeling complexes. The localization of these DLCDs to a subset of Hi-C chromatin domain boundaries that separate active versus inactive chromatin regions, as measured by two orthogonal genomic methods, suggests a distinct role for DLCDs in genome organization.

scholarly journals Histone Fold Protein Dls1p Is Required for Isw2-Dependent Chromatin Remodeling In Vivo

2004 ◽  
Vol 24 (7) ◽  
pp. 2605-2613 ◽  
Author(s):  
Audrey D. McConnell ◽  
Marnie E. Gelbart ◽  
Toshio Tsukiyama
Keyword(s):  
Dna Polymerase ◽  
Chromatin Remodeling ◽  
Dna Polymerase Epsilon ◽  
Histone Fold ◽  
Chromatin Remodeling Complex ◽  
A Subunit ◽  
Polymerase Epsilon ◽  
Higher Eukaryotes

ABSTRACT We report the identification of two new subunits of the Isw2 chromatin-remodeling complex in Saccharomyces cerevisiae. Both proteins, Dpb4p and Yjl065cp (named Dls1p), contain histone fold motifs and are homologous to the two smallest subunits of ISWI-containing CHRAC complexes in higher eukaryotes. Dpb4p is also a subunit of the DNA polymerase epsilon (polε) complex, and Dls1p is homologous to another polε subunit, Dpb3p. Therefore, these small histone fold proteins may fulfill functions that are required for both polε and Isw2 complexes. We characterized the role of Dls1p in known roles of the Isw2 complex in vivo. Transcriptional analyses reveal that the Isw2 complex requires Dls1p to various degrees at a wide variety of loci in vivo. Consistent with this, Dls1p is required for Isw2-dependent chromatin remodeling in vivo, although the requirement for this protein varies among Isw2 targets. Dls1p is likely required for functions of the Isw2 complex at steps subsequent to its interaction with chromatin, since a dls1 mutation does not affect cross-linking of Isw2 with chromatin.

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