scholarly journals A compendium of chromatin contact maps reflecting regulation by chromatin remodelers in budding yeast

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hyelim Jo ◽  
Taemook Kim ◽  
Yujin Chun ◽  
Inkyung Jung ◽  
Daeyoup Lee
Keyword(s):  
Cell Cycle ◽  
Chromatin Remodeling ◽  
Genome Organization ◽  
Budding Yeast ◽  
Catalytic Subunit ◽  
Chromatin Remodelers ◽  
3D Genome ◽  
Contact Maps ◽  
Chromosome Arm

AbstractWe herein employ in situ Hi-C with an auxin-inducible degron (AID) system to examine the effect of chromatin remodeling on 3D genome organization in yeast. Eight selected ATP-dependent chromatin remodelers representing various subfamilies contribute to 3D genome organization differently. Among the studied remodelers, the temporary depletions of Chd1p, Swr1p, and Sth1p (a catalytic subunit of the Remodeling the Structure of Chromatin [RSC] complex) cause the most significant defects in intra-chromosomal contacts, and the regulatory roles of these three remodelers in 3D genome organization differ depending on the chromosomal context and cell cycle stage. Furthermore, even though Chd1p and Isw1p are known to share functional similarities/redundancies, their depletions lead to distinct effects on 3D structures. The RSC and cohesin complexes also differentially modulate 3D genome organization within chromosome arm regions, whereas RSC appears to support the function of cohesin in centromeric clustering at G2 phase. Our work suggests that the ATP-dependent chromatin remodelers control the 3D genome organization of yeast through their chromatin-remodeling activities.

scholarly journals HP1 drives de novo 3D genome reorganization in early Drosophila embryos

Nature ◽  
2021 ◽  
Author(s):  
Fides Zenk ◽  
Yinxiu Zhan ◽  
Pavel Kos ◽  
Eva Löser ◽  
Nazerke Atinbayeva ◽  
...  
Keyword(s):  
Genome Organization ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Early Embryo ◽  
Heterochromatin Protein ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Genome Reorganization

AbstractFundamental features of 3D genome organization are established de novo in the early embryo, including clustering of pericentromeric regions, the folding of chromosome arms and the segregation of chromosomes into active (A-) and inactive (B-) compartments. However, the molecular mechanisms that drive de novo organization remain unknown1,2. Here, by combining chromosome conformation capture (Hi-C), chromatin immunoprecipitation with high-throughput sequencing (ChIP–seq), 3D DNA fluorescence in situ hybridization (3D DNA FISH) and polymer simulations, we show that heterochromatin protein 1a (HP1a) is essential for de novo 3D genome organization during Drosophila early development. The binding of HP1a at pericentromeric heterochromatin is required to establish clustering of pericentromeric regions. Moreover, HP1a binding within chromosome arms is responsible for overall chromosome folding and has an important role in the formation of B-compartment regions. However, depletion of HP1a does not affect the A-compartment, which suggests that a different molecular mechanism segregates active chromosome regions. Our work identifies HP1a as an epigenetic regulator that is involved in establishing the global structure of the genome in the early embryo.

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 β-actin dependent chromatin remodeling mediates compartment level changes in 3D genome architecture

2020 ◽  
Author(s):  
Syed Raza Mahmood ◽  
Xin Xie ◽  
Nadine Hosny El Said ◽  
Kristin C. Gunsalus ◽  
Piergiorgio Percipalle
Keyword(s):  
Chromatin Remodeling ◽  
Genomic Analysis ◽  
Chromatin Accessibility ◽  
Genome Architecture ◽  
Dependent Manner ◽  
Chromatin Remodelers ◽  
3D Genome ◽  
Polycomb Proteins ◽  
Crucial Component ◽  
Development And Differentiation

Abstractβ-actin is a crucial component of several chromatin remodeling complexes that control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes (PRCs). While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can affect the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2 in a dosage-dependent manner. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversible changes in 3D genome architecture. Our findings support a novel role for β-actin-dependent chromatin remodeling in shaping the chromatin landscape and regulating genes involved in development and differentiation.

scholarly journals β-actin dependent chromatin remodeling mediates compartment level changes in 3D genome architecture

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Syed Raza Mahmood ◽  
Xin Xie ◽  
Nadine Hosny El Said ◽  
Tomas Venit ◽  
Kristin C. Gunsalus ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Genomic Analysis ◽  
Chromatin Accessibility ◽  
Genome Architecture ◽  
Chromatin Remodelers ◽  
3D Genome ◽  
Polycomb Proteins ◽  
Crucial Component ◽  
Development And Differentiation

Abstractβ-actin is a crucial component of several chromatin remodeling complexes that control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes (PRCs). While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can induce changes in chromatin structure by affecting the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversible changes in 3D genome architecture. Our findings reveal that β-actin-dependent chromatin remodeling plays a role in shaping the chromatin landscape and influences the regulation of genes involved in development and differentiation.

scholarly journals At the Crossroad of Gene Regulation and Genome Organization: Potential Roles for ATP-Dependent Chromatin Remodelers in the Regulation of CTCF-Mediated 3D Architecture

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 272
Author(s):  
Aktan Alpsoy ◽  
Surbhi Sood ◽  
Emily C. Dykhuizen
Keyword(s):  
Genome Organization ◽  
Three Dimensional ◽  
Chromatin Remodelers ◽  
3D Genome ◽  
Quiescent Cells ◽  
Damage Repair ◽  
Architectural Proteins ◽  
3D Architecture ◽  
Specific Factors ◽  
Hierarchical Folding

In higher order organisms, the genome is assembled into a protein-dense structure called chromatin. Chromatin is spatially organized in the nucleus through hierarchical folding, which is tightly regulated both in cycling cells and quiescent cells. Assembly and folding are not one-time events in a cell’s lifetime; rather, they are subject to dynamic shifts to allow changes in transcription, DNA replication, or DNA damage repair. Chromatin is regulated at many levels, and recent tools have permitted the elucidation of specific factors involved in the maintenance and regulation of the three-dimensional (3D) genome organization. In this review/perspective, we aim to cover the potential, but relatively unelucidated, crosstalk between 3D genome architecture and the ATP-dependent chromatin remodelers with a specific focus on how the architectural proteins CTCF and cohesin are regulated by chromatin remodeling.

scholarly journals Biop-C: A Method for Chromatin Interactome Analysis of Solid Cancer Needle Biopsy Samples

2021 ◽  
Author(s):  
Sambhavi Animesh ◽  
Ruchi Choudhary ◽  
Xin Yi Ng ◽  
Joshua Kai Xun Tay ◽  
Wan-Qin Chong ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Genome Organization ◽  
Needle Biopsy ◽  
Nasopharyngeal Cancer ◽  
Chromatin Interaction ◽  
Solid Cancer ◽  
Heat Maps ◽  
3D Genome ◽  
Topologically Associated Domains

AbstractA major challenge in understanding the 3D genome organization of cancer samples is the lack of a method adapted to solid cancer needle biopsy samples. Here we developed Biop-C, a modified in situ Hi-C method, and applied it to characterize three nasopharyngeal cancer patient samples. We identified Topologically-Associated Domains (TADs), chromatin interaction loops, and Frequently Interacting regions (FIREs) at key oncogenes in nasopharyngeal cancer from Biop-C heat maps. Our results demonstrate the utility of our Biop-C method in investigating the 3D genome organization in solid cancers, and the importance of 3D genome organization in regulating oncogenes in nasopharyngeal cancer.

scholarly journals Tracking multiple genomic elements using correlative CRISPR imaging and sequential DNA FISH

2017 ◽  
Author(s):  
J. Guan ◽  
H. Liu ◽  
X. Shi ◽  
S. Feng ◽  
B. Huang
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Genome Organization ◽  
Live Imaging ◽  
Color Palette ◽  
Antibody Staining ◽  
Rna Fish ◽  
Protein Imaging ◽  
A Cell

AbstractLive imaging of genome has offered important insights into the dynamics of the genome organization and gene expression. The demand to image simultaneously multiple genomic loci has prompted a flurry of exciting advances in multi-color CRISPR imaging, although color-based multiplexing is limited by the need for spectrally distinct fluorophores. Here we introduce an approach to achieve highly multiplexed live recording via correlative CRISPR imaging and sequential DNA fluorescence in situ hybridization (FISH). This approach first performs one-color live imaging of multiple genomic loci and then uses sequential rounds of DNA FISH to determine the loci identity. We have optimized the FISH protocol so that each round is complete in 1 min, demonstrating the identification of 7 genomic elements and the capability to sustain reversible staining and washing for up to 20 rounds. We have also developed a correlation-based algorithm to faithfully register live and FISH images. Our approach keeps the rest of the color palette open to image other cellular phenomena of interest, as demonstrated by our simultaneous live imaging of genomic loci together with a cell cycle reporter. Furthermore, the algorithm to register faithfully between live and fixed imaging is directly transferrable to other systems such as multiplex RNA imaging with RNA-FISH and multiplex protein imaging with antibody-staining.

scholarly journals Members of the NAP/SET family of proteins interact specifically with B-type cyclins.

1995 ◽  
Vol 130 (3) ◽  
pp. 661-673 ◽  
Author(s):  
D R Kellogg ◽  
A Kikuchi ◽  
T Fujii-Nakata ◽  
C W Turck ◽  
A W Murray
Keyword(s):  
Cell Cycle ◽  
Fusion Protein ◽  
Affinity Chromatography ◽  
Budding Yeast ◽  
Cyclin A ◽  
Xenopus Embryo ◽  
Catalytic Subunit ◽  
Cyclin B ◽  
Cyclin Dependent Kinase ◽  
Do So

Cyclin-dependent kinase complexes that contain the same catalytic subunit are able to induce different events at different times during the cell cycle, but the mechanisms by which they do so remain largely unknown. To address this problem, we have used affinity chromatography to identify proteins that bind specifically to mitotic cyclins, with the goal of finding proteins that interact with mitotic cyclins to carry out the events of mitosis. This approach has led to the identification of a 60-kD protein called NAP1 that interacts specifically with members of the cyclin B family. This interaction has been highly conserved during evolution: NAP1 in the Xenopus embryo interacts with cyclins B1 and B2, but not with cyclin A, and the S. cerevisiae homolog of NAP1 interacts with Clb2 but not with Clb3. Genetic experiments in budding yeast indicate that NAP1 plays an important role in the function of Clb2, while biochemical experiments demonstrate that purified NAP1 can be phosphorylated by cyclin B/p34cdc2 kinase complexes, but not by cyclin A/p34cdc2 kinase complexes. These results suggest that NAP1 is a protein involved in the specific functions of cyclin B/p34cdc2 kinase complexes. In addition to NAP1, we found a 43-kD protein in Xenopus that is homologous to NAP1 and also interacts specifically with B-type cyclins. This protein is the Xenopus homolog of the human SET protein, which was previously identified as part of a putative oncogenic fusion protein (Von Lindern et al., 1992).

scholarly journals The chromatin remodeler SMARCD3 regulates cell cycle progression and its expression predicts survival outcome in ER+ breast cancer

2019 ◽  
Author(s):  
Romain Tropée ◽  
Bárbara de la Peña Avalos ◽  
Madeline Gough ◽  
Cameron Snell ◽  
Pascal H.G. Duijf ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Patient ◽  
Breast Cancer Patient ◽  
Cancer Patients ◽  
Chromatin Remodeling ◽  
Survival Rates ◽  
Transcriptional Networks ◽  
Breast Cancer Patients ◽  
Chromatin Remodelers

AbstractChromatin remodeling plays an essential role in regulating transcriptional networks and timing of gene expression. Chromatin remodelers such as SWItch/Sucrose Non-Fermentable (SWI/SNF) harbor many protein components, with the catalytic subunit providing ATPase activity to displace histones along or from the DNA molecules, and associated subunits ensuring tissue specificity and transcriptional or co-transcriptional activities. Mutations in several of the SWI/SNF subunits have been linked to cancer. Here, we describe how SMARCD3/Baf60c expression is associated with hormone positive (ER+) breast cancer. The level SMARCD3, as detected by immunohistochemistry in breast cancer patient samples, is correlated with differential long-term disease-free survival. In contrast, the expression level of SMARCD1/Baf60a and SMARCD2/Baf60b, which are mutually exclusive within the SWI/SNF complex and have a partially redundant function, lacks predictive value in breast cancer patient samples. Lower proliferation rates are observed in SMARCD3 depleted cells, which reflects a failure to fully progress through G2/M, and an increase in endoreplication. In the absence of SMARCD3, p21 accumulates in cells but does not halt the cell cycle, and DNA damage accumulates and remains unrepaired. Taken together, our data begin to explain why ER+ breast cancer patients with low SMARCD3 expressing tumors exhibit reduced survival rates compared to patients expressing normal or higher levels of SMARCD3. SMARCD3 might act as a tumor suppressor role through regulation of cell cycle checkpoints and could be a reliable and specific breast cancer prognostic biomarker.SignificanceMutations in chromatin remodelers are a leading cause of cancer. Estrogen Receptor positive (ER+) breast cancers represent approximately 80% of all cases diagnosed. Although these tumors can be treated with hormone therapy, most breast cancer fatalities occur in ER+ breast cancer patients, due to metastasis. Low expression of SMARCD3 in ER+ cancer is associated with diminished survival rates. As such, SMARCD3 could be used as a predictive biomarker for survival. In addition, we have identified a role for SMARCD3 in the cell cycle, which could at least partially explain its protective role in breast cancer. While catalytic subunits are often viewed as the major components in chromatin remodeling function, we show here new evidence that mutations or silencing of SMARCD3 may also contribute to genomic instability and thus development of breast cancer.

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