scholarly journals Rapid depletion of CTCF and cohesin proteins reveals dynamic features of chromosome architecture

2021 ◽  
Author(s):  
Ning Qing Liu ◽  
Mikhail Magnitov ◽  
Marijne Schijns ◽  
Tom van Schaik ◽  
Robin H. van der Weide ◽  
...  
Keyword(s):  
Nuclear Lamina ◽  
Gene Clusters ◽  
Gene Clustering ◽  
Chromosome Organization ◽  
Open Chromatin ◽  
List Type ◽  
Dynamic Features ◽  
Chromosome Architecture ◽  
Architectural Feature ◽  
Active Genes

SUMMARYThe interphase genome is mainly shaped by cohesin-mediated loop extrusion and cohesin-independent compartmentalization. Extrusion is a dynamic process of cohesin loading, loop extension and release. Cohesin release is mediated by WAPL. Loss of WAPL leads to the formation of longer loops and counters compartmentalization. The dynamics of these changes in chromosome organization have been unclear. We have used acute depletion of WAPL to show that within six hours cohesin accumulates at CTCF-bound loop anchors and extended loops are formed. When we deplete WAPL and CTCF simultaneously, new loops are formed between active genes. Surprisingly, active gene clustering is independent of cohesin. Stabilization of cohesin on chromatin leads to a decrease in compartmentalization, which is rapidly restored by depletion of cohesin. Our analyses show that loop extrusion counters compartmentalization and plays a central role in many aspects of chromosome organization.HIGHLIGHTSCohesin accumulates at CTCF-mediated chromatin loop anchors following WAPL depletion.Actively transcribed genes form long-range gene clusters independent of the cohesin complex.Plumes are a novel architectural feature of juxtaposed DNA formed by cohesin at open chromatin islands.Chromosome compartmentalization can be uncoupled from nuclear lamina interactions.

The nuclear lamina and heterochromatin: a complex relationship

2011 ◽  
Vol 39 (6) ◽  
pp. 1705-1709 ◽  
Author(s):  
Erin M. Bank ◽  
Yosef Gruenbaum
Keyword(s):  
Nuclear Periphery ◽  
Gene Activation ◽  
Nuclear Lamina ◽  
Current Evidence ◽  
Specific Gene ◽  
Nuclear Interior ◽  
Gene Retention ◽  
Gene Positioning ◽  
Review Current ◽  
Active Genes

In metazoan cells, the heterochromatin is generally localized at the nuclear periphery, whereas active genes are preferentially found in the nuclear interior. In the present paper, we review current evidence showing that components of the nuclear lamina interact directly with heterochromatin, which implicates the nuclear lamina in a mechanism of specific gene retention at the nuclear periphery and release to the nuclear interior upon gene activation. We also discuss recent data showing that mutations in lamin proteins affect gene positioning and expression, providing a potential mechanism for how these mutations lead to tissue-specific diseases.

scholarly journals Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains

2003 ◽  
Vol 162 (6) ◽  
pp. 981-990 ◽  
Author(s):  
Lindsay S. Shopland ◽  
Carol V. Johnson ◽  
Meg Byron ◽  
John McNeil ◽  
Jeanne B. Lawrence
Keyword(s):  
Gene Clustering ◽  
Splicing Factors ◽  
Metabolic Factors ◽  
Highly Active ◽  
Morphometric Analyses ◽  
Common Domain ◽  
Chromosomal Bands ◽  
Chromosome Bands ◽  
Active Genes ◽  
Nuclear Clustering

Typically, eukaryotic nuclei contain 10–30 prominent domains (referred to here as SC-35 domains) that are concentrated in mRNA metabolic factors. Here, we show that multiple specific genes cluster around a common SC-35 domain, which contains multiple mRNAs. Nonsyntenic genes are capable of associating with a common domain, but domain “choice” appears random, even for two coordinately expressed genes. Active genes widely separated on different chromosome arms associate with the same domain frequently, assorting randomly into the 3–4 subregions of the chromosome periphery that contact a domain. Most importantly, visualization of six individual chromosome bands showed that large genomic segments (∼5 Mb) have striking differences in organization relative to domains. Certain bands showed extensive contact, often aligning with or encircling an SC-35 domain, whereas others did not. All three gene-rich reverse bands showed this more than the gene-poor Giemsa dark bands, and morphometric analyses demonstrated statistically significant differences. Similarly, late-replicating DNA generally avoids SC-35 domains. These findings suggest a functional rationale for gene clustering in chromosomal bands, which relates to nuclear clustering of genes with SC-35 domains. Rather than random reservoirs of splicing factors, or factors accumulated on an individual highly active gene, we propose a model of SC-35 domains as functional centers for a multitude of clustered genes, forming local euchromatic “neighborhoods.”

scholarly journals Application of Gene Shaving and Mixture Models to Cluster Microarray Gene Expression Data

2007 ◽  
Vol 5 ◽  
pp. 117693510700500
Author(s):  
K-A. Do ◽  
G.J. McLachlan ◽  
R. Bean ◽  
S. Wen
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Gene Clusters ◽  
Gene Clustering ◽  
Expression Data ◽  
Colon Tissue ◽  
Data Set ◽  
Tissue Samples ◽  
Gene Shaving

Researchers are frequently faced with the analysis of microarray data of a relatively large number of genes using a small number of tissue samples. We examine the application of two statistical methods for clustering such microarray expression data: EMMIX-GENE and GeneClust. EMMIX-GENE is a mixture-model based clustering approach, designed primarily to cluster tissue samples on the basis of the genes. GeneClust is an implementation of the gene shaving methodology, motivated by research to identify distinct sets of genes for which variation in expression could be related to a biological property of the tissue samples. We illustrate the use of these two methods in the analysis of Affymetrix oligonucleotide arrays of well-known data sets from colon tissue samples with and without tumors, and of tumor tissue samples from patients with leukemia. Although the two approaches have been developed from different perspectives, the results demonstrate a clear correspondence between gene clusters produced by GeneClust and EMMIX-GENE for the colon tissue data. It is demonstrated, for the case of ribosomal proteins and smooth muscle genes in the colon data set, that both methods can classify genes into co-regulated families. It is further demonstrated that tissue types (tumor and normal) can be separated on the basis of subtle distributed patterns of genes. Application to the leukemia tissue data produces a division of tissues corresponding closely to the external classification, acute myeloid meukemia (AML) and acute lymphoblastic leukemia (ALL), for both methods. In addition, we also identify genes specific for the subgroup of ALL-Tcell samples. Overall, we find that the gene shaving method produces gene clusters at great speed; allows variable cluster sizes and can incorporate partial or full supervision; and finds clusters of genes in which the gene expression varies greatly over the tissue samples while maintaining a high level of coherence between the gene expression profiles. The intent of the EMMIX-GENE method is to cluster the tissue samples. It performs a filtering step that results in a subset of relevant genes, followed by gene clustering, and then tissue clustering, and is favorable in its accuracy of ranking the clusters produced.

scholarly journals Trichoderma reesei complete genome sequence, repeat-induced point mutation and partitioning of CAZyme gene clusters

2017 ◽  
Author(s):  
Wan-Chen Li ◽  
Chien-Hao Huang ◽  
Chia-Ling Chen ◽  
Yu-Chien Chuang ◽  
Shu-Yun Tung ◽  
...  
Keyword(s):  
Point Mutation ◽  
Trichoderma Reesei ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Gene Clusters ◽  
Ancestral Gene ◽  
Chromosome Architecture ◽  
Genome Wide ◽  
Repeat Induced Point Mutation

AbstractTrichoderma reesei (Ascomycota, Pezizomycotina) QM6a is a model fungus for a broad spectrum of physiological phenomena, including plant cell wall degradation, industrial production of enzymes, light responses, conidiation, sexual development, polyketide biosynthesis and plant-fungal interactions. The genomes of QM6a and its high-enzyme producing mutants have been sequenced by second-generation-sequencing methods and are publicly available from the Joint Genome Institute (JGI). While these genome sequences have offered useful information for genomic and transcriptomic studies, their limitations and especially their short read lengths make them poorly suited for some particular biological problems, including assembly, genome-wide determination of chromosome architecture and genetic modification or engineering. We integrated Pacific Biosciences and Illumina sequencing platforms for the highest-quality genome assembly yet achieved, revealing seven telomere-to-telomere chromosomes (34,922,528 bp; 10877 genes) with 1630 newly-predicted genes and >1.5 Mb of new sequences. Most new sequences are located on AT-rich blocks, including 7 centromeres, 14 subtelomeres and 2329 interspersed AT-rich blocks. The seven QM6a centromeres separately consist of 24 conserved repeats and 37 putative centromere-encoded genes. These findings open up a new perspective for future centromere and chromosome architecture studies. Next, we demonstrate that sexual crossing readily induced cytosine-to-thymine point mutations on both tandem and unlinked duplicated sequences. We also show by bioinformatic analysis that Trichoderma reesei has evolved a robust repeat-induced point mutation (RIP) system to accumulate AT-rich sequences, with longer AT-rich blocks having more RIP mutations. The widespread distribution of AT-rich blocks correlates genome-wide partitions with gene clusters, explaining why clustering of genes has been reported to not influence gene expression in Trichoderma reesei. Compartmentation of ancestral gene clusters by AT-rich blocks might promote flexibilities that are evolutionarily advantageous in this fungus’ soil habitats and other natural environments. Our analyses, together with the complete genome sequence, provide a better blueprint for biotechnological and industrial applications.

scholarly journals Genome-wide maps of nucleolus interactions reveal distinct layers of repressive chromatin domains

2020 ◽  
Author(s):  
Cristiana Bersaglieri ◽  
Jelena Kresoja-Rakic ◽  
Shivani Gupta ◽  
Dominik Bär ◽  
Rostyslav Kuzyakiv ◽  
...  
Keyword(s):  
Nuclear Periphery ◽  
Interaction Strength ◽  
Nuclear Lamina ◽  
Nuclear Space ◽  
Chromosome Architecture ◽  
Neural Genes ◽  
Repressive Chromatin ◽  
Genome Wide ◽  
Nuclear Environment

AbstractEukaryotic chromosomes are folded into hierarchical domains, enabling the organization of the genome into functional compartments. Nuclear periphery and nucleolus are two nuclear landmarks thought to contribute to repressive chromosome architecture. However, while the role of nuclear lamina (NL) in genome organization has been well documented, the function of the nucleolus remains under-investigated due to the lack of methods for genome-wide maps of nucleolar associated domains (NADs). Here we established a method based on a Dam-fused engineered nucleolar histone H2B that marks DNA contacting the nucleolus. NAD-maps of ESCs and neural progenitors revealed layers of genome compartmentalization with distinct, repressive chromatin states based on the interaction with the nucleolus, NL, or both. NADs showed higher H3K9me2 and lower H3K27me3 content than regions exclusively interacting with NL. Upon ESC differentiation, chromosomes around the nucleolus acquire a more compact, rigid architecture whereas NADs specific for ESCs decrease their interaction strength within the repressive B-compartment strength, unlocking neural genes from repressive nuclear environment. The methodologies here developed will make possible to include the contribution of the nucleolus in future studies investigating the relationship between nuclear space and genome function.

scholarly journals PRC1-dependent compaction of Hox gene clusters prevents transcriptional derepression during early Drosophila embryogenesis

2018 ◽  
Author(s):  
Thierry Cheutin ◽  
Giacomo Cavalli
Keyword(s):  
Gene Expression ◽  
Gene Clusters ◽  
Higher Order ◽  
Early Embryogenesis ◽  
Open Chromatin ◽  
Structural Constraints ◽  
Chromatin Domains ◽  
Hox Gene ◽  
Stage Of Development ◽  
Chromatin Folding

Summary paragraphPolycomb-group (PcG) proteins are conserved chromatin factors that maintain the silencing of key developmental genes, notably the Hox gene clusters, outside of their expression domains [1-3]. Polycomb repressive complex 2 (PRC2) trimethylates lysine K27 of histone H3 [4], and PRC1 collaborates with PRC2 in gene silencing. Genome-wide studies have revealed large H3K27me3 chromatin domains bound by PcG proteins, and Polycomb domains fold into distinct nuclear structures [5-9]. Although PRC1 is involved in chromatin compaction [10-16], it is unknown whether PRC1-dependent transcriptional silencing is a consequence of its role on higher-order chromatin folding. This is because depletion of PRC1 proteins typically induces both chromatin unfolding and ectopic transcription, and ectopic transcription can open chromatin by itself. To disentangle these two components, we analysed the temporal effects of two PRC1 proteins, Polyhomeotic (Ph) and Polycomb (Pc), on Hox gene clusters during Drosophila embryogenesis. We show that the absence of Ph or Pc affects the higher-order chromatin folding of Hox clusters prior to ectopic Hox gene transcription, demonstrating that PRC1 primary function during early embryogenesis is to compact its target chromatin. During later embryogenesis, we observed further chromatin opening at Hox complexes in both Ph and Pc mutants, which was coupled to strong deregulation of Hox genes at this stage of development. Moreover, the differential effects of Ph and Pc on Hox cluster folding matches the differences in ectopic Hox gene expression observed in these two mutants, suggesting that the degree of Hox derepression in PcG mutants depends on the degree of structural constraints imposed by each PcG component. In summary, our data demonstrate that binding of PRC1 to large genomic domains during early embryogenesis induces the formation of compact chromatin to prevent ectopic gene expression at later time-points. Thus, epigenetic mechanisms such as Polycomb mediated silencing act by folding chromatin domains and impose an architectural layer to gene regulation.

scholarly journals Plant Metabolic Gene Clusters: Evolution, Organization, and Their Applications in Synthetic Biology

2021 ◽  
Vol 12 ◽  
Author(s):  
Revuru Bharadwaj ◽  
Sarma R. Kumar ◽  
Ashutosh Sharma ◽  
Ramalingam Sathishkumar
Keyword(s):  
Synthetic Biology ◽  
Functional Characterization ◽  
Gene Clusters ◽  
Gene Clustering ◽  
Specific Gene ◽  
Gene Duplications ◽  
Ecological Functions ◽  
Specialized Metabolites ◽  
Coordinated Expression

Plants are a remarkable source of high-value specialized metabolites having significant physiological and ecological functions. Genes responsible for synthesizing specialized metabolites are often clustered together for a coordinated expression, which is commonly observed in bacteria and filamentous fungi. Similar to prokaryotic gene clustering, plants do have gene clusters encoding enzymes involved in the biosynthesis of specialized metabolites. More than 20 gene clusters involved in the biosynthesis of diverse metabolites have been identified across the plant kingdom. Recent studies demonstrate that gene clusters are evolved through gene duplications and neofunctionalization of primary metabolic pathway genes. Often, these clusters are tightly regulated at nucleosome level. The prevalence of gene clusters related to specialized metabolites offers an attractive possibility of an untapped source of highly useful biomolecules. Accordingly, the identification and functional characterization of novel biosynthetic pathways in plants need to be worked out. In this review, we summarize insights into the evolution of gene clusters and discuss the organization and importance of specific gene clusters in the biosynthesis of specialized metabolites. Regulatory mechanisms which operate in some of the important gene clusters have also been briefly described. Finally, we highlight the importance of gene clusters to develop future metabolic engineering or synthetic biology strategies for the heterologous production of novel metabolites.

scholarly journals Dynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Virginia S. Lioy ◽  
Jean-Noël Lorenzi ◽  
Soumaya Najah ◽  
Thibault Poinsignon ◽  
Hervé Leh ◽  
...  
Keyword(s):  
Chromosome Structure ◽  
Gene Clusters ◽  
Structural Features ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Linear Chromosome ◽  
Chromosome Architecture ◽  
Specialized Metabolites ◽  
Streptomyces Ambofaciens ◽  
Core Genes

AbstractBacteria of the genus Streptomyces are prolific producers of specialized metabolites, including antibiotics. The linear chromosome includes a central region harboring core genes, as well as extremities enriched in specialized metabolite biosynthetic gene clusters. Here, we show that chromosome structure in Streptomyces ambofaciens correlates with genetic compartmentalization during exponential phase. Conserved, large and highly transcribed genes form boundaries that segment the central part of the chromosome into domains, whereas the terminal ends tend to be transcriptionally quiescent compartments with different structural features. The onset of metabolic differentiation is accompanied by a rearrangement of chromosome architecture, from a rather ‘open’ to a ‘closed’ conformation, in which highly expressed specialized metabolite biosynthetic genes form new boundaries. Thus, our results indicate that the linear chromosome of S. ambofaciens is partitioned into structurally distinct entities, suggesting a link between chromosome folding, gene expression and genome evolution.

scholarly journals Active and repressed biosynthetic gene clusters have spatially distinct chromosome states

2020 ◽  
Vol 117 (24) ◽  
pp. 13800-13809 ◽  
Author(s):  
Hans-Wilhelm Nützmann ◽  
Daniel Doerr ◽  
América Ramírez-Colmenero ◽  
Jesús Emiliano Sotelo-Fonseca ◽  
Eva Wegel ◽  
...  
Keyword(s):  
Nuclear Periphery ◽  
Gene Clusters ◽  
Gene Location ◽  
Gene Clustering ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Chromosome Conformation ◽  
Topological Domains ◽  
Eukaryotic Genes ◽  
Capture Techniques

While colocalization within a bacterial operon enables coexpression of the constituent genes, the mechanistic logic of clustering of nonhomologous monocistronic genes in eukaryotes is not immediately obvious. Biosynthetic gene clusters that encode pathways for specialized metabolites are an exception to the classical eukaryote rule of random gene location and provide paradigmatic exemplars with which to understand eukaryotic cluster dynamics and regulation. Here, using 3C, Hi-C, and Capture Hi-C (CHi-C) organ-specific chromosome conformation capture techniques along with high-resolution microscopy, we investigate how chromosome topology relates to transcriptional activity of clustered biosynthetic pathway genes inArabidopsis thaliana. Our analyses reveal that biosynthetic gene clusters are embedded in local hot spots of 3D contacts that segregate cluster regions from the surrounding chromosome environment. The spatial conformation of these cluster-associated domains differs between transcriptionally active and silenced clusters. We further show that silenced clusters associate with heterochromatic chromosomal domains toward the periphery of the nucleus, while transcriptionally active clusters relocate away from the nuclear periphery. Examination of chromosome structure at unrelated clusters in maize, rice, and tomato indicates that integration of clustered pathway genes into distinct topological domains is a common feature in plant genomes. Our results shed light on the potential mechanisms that constrain coexpression within clusters of nonhomologous eukaryotic genes and suggest that gene clustering in the one-dimensional chromosome is accompanied by compartmentalization of the 3D chromosome.

scholarly journals Lineage-tracing and translatomic analysis of damage-inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration

PLoS Biology ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. e3001445
Author(s):  
Tomokatsu Udagawa ◽  
Patrick J. Atkinson ◽  
Beatrice Milon ◽  
Julia M. Abitbol ◽  
Yang Song ◽  
...  
Keyword(s):  
Clustering Algorithms ◽  
Organ Of Corti ◽  
Gene Clusters ◽  
Lineage Tracing ◽  
Calcium Transients ◽  
Gene Clustering ◽  
Supporting Cells ◽  
Hearing Function ◽  
Cochlear Supporting Cells

Cochlear supporting cells (SCs) are glia-like cells critical for hearing function. In the neonatal cochlea, the greater epithelial ridge (GER) is a mitotically quiescent and transient organ, which has been shown to nonmitotically regenerate SCs. Here, we ablated Lgr5+ SCs using Lgr5-DTR mice and found mitotic regeneration of SCs by GER cells in vivo. With lineage tracing, we show that the GER houses progenitor cells that robustly divide and migrate into the organ of Corti to replenish ablated SCs. Regenerated SCs display coordinated calcium transients, markers of the SC subtype inner phalangeal cells, and survive in the mature cochlea. Via RiboTag, RNA-sequencing, and gene clustering algorithms, we reveal 11 distinct gene clusters comprising markers of the quiescent and damaged GER, and damage-responsive genes driving cell migration and mitotic regeneration. Together, our study characterizes GER cells as mitotic progenitors with regenerative potential and unveils their quiescent and damaged translatomes.

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