scholarly journals Exploring Mammalian Genome within Phase-Separated Nuclear Bodies: Experimental Methods and Implications for Gene Expression

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1049 ◽  
Author(s):  
Annick Lesne ◽  
Marie-Odile Baudement ◽  
Cosette Rebouissou ◽  
Thierry Forné
Keyword(s):  
Gene Expression ◽  
Self Assembly ◽  
Genome Organization ◽  
Physical Nature ◽  
Mammalian Genome ◽  
Nuclear Bodies ◽  
Control Of Gene Expression ◽  
Chromatin Interactions ◽  
Nuclear Structures ◽  
Genomic Regions

The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active/inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase-separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.

scholarly journals Exploring Mammalian Genome within Phase-Separated Nuclear Bodies: Experimental Methods and Implications for Gene Expression

2019 ◽  
Author(s):  
Annick Lesne ◽  
Marie-Odile Baudement ◽  
Cosette Rebouissou ◽  
Thierry Forné
Keyword(s):  
Gene Expression ◽  
Self Assembly ◽  
Genome Organization ◽  
Physical Nature ◽  
Mammalian Genome ◽  
Nuclear Bodies ◽  
Control Of Gene Expression ◽  
Chromatin Interactions ◽  
Nuclear Structures ◽  
Genomic Regions

The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active / inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.

scholarly journals Exploring Mammalian Genome within Phase-Separated Nuclear Bodies: Implications for the Regulation of Gene Expression

2019 ◽  
Author(s):  
Annick Lesne ◽  
Marie-Odile Baudement ◽  
Cosette Rebouissou ◽  
Thierry Forné
Keyword(s):  
Gene Expression ◽  
Self Assembly ◽  
Genome Organization ◽  
Regulation Of Gene Expression ◽  
Physical Nature ◽  
Mammalian Genome ◽  
Nuclear Bodies ◽  
Control Of Gene Expression ◽  
Nuclear Structures ◽  
Genomic Regions

The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active / inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), designed to identify chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.

scholarly journals Exploring Mammalian Genome within Phase-Separated Nuclear Bodies: Implications for the Regulation of Gene Expression

2019 ◽  
Author(s):  
Annick Lesne ◽  
Marie-Odile Baudement ◽  
Cosette Rebouissou ◽  
Thierry Forné
Keyword(s):  
Gene Expression ◽  
Self Assembly ◽  
Genome Organization ◽  
Regulation Of Gene Expression ◽  
Physical Nature ◽  
Mammalian Genome ◽  
Nuclear Bodies ◽  
Control Of Gene Expression ◽  
Nuclear Structures ◽  
Genomic Regions

The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active / inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.

scholarly journals H3K27me3-rich genomic regions can function as silencers to repress gene expression via chromatin interactions

2019 ◽  
Author(s):  
Yichao Cai ◽  
Ying Zhang ◽  
Yan Ping Loh ◽  
Jia Qi Tng ◽  
Mei Chee Lim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Target Genes ◽  
Gene Repression ◽  
Xenograft Tumor ◽  
Regulate Gene Expression ◽  
Chromatin Interactions ◽  
Genomic Regions ◽  
Xenograft Tumor Growth ◽  
Regulate Gene

AbstractGene repression and silencers are poorly understood. We reasoned that H3K27me3-rich regions (MRRs) of the genome defined from clusters of H3K27me3 peaks may be used to identify silencers that can regulate gene expression via proximity or looping. MRRs were associated with chromatin interactions and interact preferentially with each other. MRR component removal at interaction anchors by CRISPR led to upregulation of interacting target genes, altered H3K27me3 and H3K27ac levels at interacting regions, and altered chromatin interactions. Chromatin interactions did not change at regions with high H3K27me3, but regions with low H3K27me3 and high H3K27ac levels showed changes in chromatin interactions. The MRR knockout cells also showed changes in phenotype associated with cell identity, and altered xenograft tumor growth. MRR-associated genes and long-range chromatin interactions were susceptible to H3K27me3 depletion. Our results characterized H3K27me3-rich regions and their mechanisms of functioning via looping.

scholarly journals Seed and grow: a two-step model for nuclear body biogenesis

2011 ◽  
Vol 193 (4) ◽  
pp. 605-606 ◽  
Author(s):  
Miroslav Dundr
Keyword(s):  
Gene Expression ◽  
Self Assembly ◽  
Nuclear Body ◽  
Nuclear Bodies ◽  
Genome Maintenance ◽  
Step Model ◽  
Specific Activities ◽  
Key Features ◽  
Dynamic Structures ◽  
Initial Seeding

Nuclear bodies are dynamic structures that form at sites of specific activities associated with gene expression and genome maintenance. A paper in this issue (White et al. 2011. J. Cell Biol. doi: 10.1083/jcb.201012077) highlights key features of nuclear body biogenesis and suggests a unifying model in which formation of nuclear bodies is driven by nonrandom, biologically determined initial seeding events followed by stochastic self-assembly.

scholarly journals Interplay of pericentromeric genome organization and chromatin landscape regulates the expression of Drosophila melanogaster heterochromatic genes

2019 ◽  
Author(s):  
Parna Saha ◽  
Divya Tej Sowpati ◽  
Ishanee Srivastava ◽  
Rakesh Kumar Mishra
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Genome Organization ◽  
Constitutive Heterochromatin ◽  
Pericentromeric Heterochromatin ◽  
Chromatin Interactions ◽  
Recent Developments ◽  
Epigenetic Code ◽  
Heterochromatic Genes

AbstractTranscription of heterochromatic genes residing within the constitutive heterochromatin is paradoxical to the tenets of the epigenetic code. Drosophila melanogaster heterochromatic genes serve as an excellent model system to understand the mechanisms of their transcriptional regulation. Recent developments in chromatin conformation techniques have revealed that genome organization regulates the transcriptional outputs. Thus, using 5C-seq in S2 cells, we present a detailed characterization of the hierarchical genome organization of Drosophila pericentromeric heterochromatin and its contribution to heterochromatic gene expression. We show that pericentromeric TAD borders are enriched in nuclear Matrix attachment regions while the intra-TAD interactions are mediated by various insulator binding proteins. Heterochromatic genes of similar expression levels cluster into Het TADs which indicates their transcriptional co-regulation. To elucidate how heterochromatic factors, influence the expression of heterochromatic genes, we performed 5C-seq in the HP1a or Su(var)3-9 depleted cells. HP1a or Su(var)3-9 RNAi results in perturbation of global pericentromeric TAD organization but the expression of the heterochromatic genes is minimally affected. Subset of active heterochromatic genes have been shown to have combination of HP1a/H3K9me3 with H3K36me3 at their exons. Interestingly, the knock-down of dMES-4 (H3K36 methyltransferase), downregulates expression of the heterochromatic genes. This indicates that the local chromatin interactions and the combination of heterochromatic factors (HP1a or H3K9me3) along with the H3K36me3 is crucial to drive the expression of heterochromatic genes. Furthermore, dADD1, present near the TSS of the active heterochromatic genes, can bind to both H3K9me3 or HP1a and facilitate the heterochromatic gene expression by regulating the H3K36me3 levels. Therefore, our findings provide mechanistic insights into the interplay of genome organization and chromatin factors at the pericentromeric heterochromatin that regulates Drosophila melanogaster heterochromatic gene expression.

scholarly journals AGO1 in association with NEAT1 lncRNA contributes to nuclear and 3D chromatin architecture in human cells

2019 ◽  
Author(s):  
Muhammad Shuaib ◽  
Krishna Mohan Parsi ◽  
Hideya Kawaji ◽  
Manjula Thimma ◽  
Sabir Abdu Adroub ◽  
...  
Keyword(s):  
Gene Expression ◽  
Genome Organization ◽  
Global Gene Expression ◽  
Human Cells ◽  
Nuclear Bodies ◽  
Genome Architecture ◽  
Global Changes ◽  
Active Chromatin ◽  
Altered Expression ◽  
3D Genome

AbstractAside from their roles in the cytoplasm, RNA-interference components have been reported to localize also in the nucleus of human cells. In particular, AGO1 associates with active chromatin and appears to influence global gene expression. However, the mechanistic aspects remain elusive. Here, we identify AGO1 as a paraspeckle component that in combination with the NEAT1 lncRNA maintains 3D genome architecture. We demonstrate that AGO1 interacts with NEAT1 lncRNA and its depletion affects NEAT1 expression and the formation of paraspeckles. By Hi-C analysis in AGO1 knockdown cells, we observed global changes in chromatin organization, including TADs configuration, and A/B compartment mixing. Consistently, distinct groups of genes located within the differential interacting loci showed altered expression upon AGO1 depletion. NEAT1 knockout cells displayed similar changes in TADs and higher-order A/B compartmentalization. We propose that AGO1 in association with NEAT1 lncRNA can act as a scaffold that bridges chromatin and nuclear bodies to regulate genome organization and gene expression in human cells.

scholarly journals Chromatin information content landscapes inform transcription factor and DNA interactions

2019 ◽  
Author(s):  
Ricardo D’Oliveira Albanus ◽  
Yasuhiro Kyono ◽  
John Hensley ◽  
Arushi Varshney ◽  
Peter Orchard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Information Content ◽  
Binding Sites ◽  
Genome Organization ◽  
Specific Protein ◽  
Chromatin Accessibility ◽  
Human Tissues ◽  
Dna Interactions ◽  
Cell State ◽  
Chromatin Interactions

AbstractInteractions between transcription factors (TFs) and chromatin are fundamental to genome organization and regulation and, ultimately, cell state. Here, we use information theory to measure signatures of TF-chromatin interactions encoded in the patterns of the accessible genome, which we call chromatin information enrichment (CIE). We calculate CIE for hundreds of TF motifs across human tissues and identify two classes: low and high CIE. The 10-20% of TF motifs with high CIE associate with higher protein-DNA residence time, including different binding sites subclasses of the same TF, increased nucleosome phasing, specific protein domains, and the genetic control of both gene expression and chromatin accessibility. These results show that variations in the information content of chromatin architecture reflect functional biological variation, with implications for cell state dynamics and memory.

scholarly journals Chromatin information content landscapes inform transcription factor and DNA interactions

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ricardo D’Oliveira Albanus ◽  
Yasuhiro Kyono ◽  
John Hensley ◽  
Arushi Varshney ◽  
Peter Orchard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Information Theory ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Genome Organization ◽  
Specific Protein ◽  
Chromatin Accessibility ◽  
Dna Interactions ◽  
Cell State ◽  
Chromatin Interactions

AbstractInteractions between transcription factors and chromatin are fundamental to genome organization and regulation and, ultimately, cell state. Here, we use information theory to measure signatures of organized chromatin resulting from transcription factor-chromatin interactions encoded in the patterns of the accessible genome, which we term chromatin information enrichment (CIE). We calculate CIE for hundreds of transcription factor motifs across human samples and identify two classes: low and high CIE. The 10–20% of common and tissue-specific high CIE transcription factor motifs, associate with higher protein–DNA residence time, including different binding site subclasses of the same transcription factor, increased nucleosome phasing, specific protein domains, and the genetic control of both chromatin accessibility and gene expression. These results show that variations in the information encoded in chromatin architecture reflect functional biological variation, with implications for cell state dynamics and memory.

scholarly journals Control of gene expression by modulated self-assembly

2011 ◽  
Vol 39 (16) ◽  
pp. 6854-6863 ◽  
Author(s):  
Jose M. G. Vilar ◽  
Leonor Saiz
Keyword(s):  
Gene Expression ◽  
Self Assembly ◽  
Control Of Gene Expression
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