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Stochastic genome - nuclear lamina contacts are linked to histone H3K9 dimethylation (methylation data)

ABSTRACT: The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina-associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a novel 'molecular contact memory' approach. In each interphase nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL correlates with their degree of H3K9 dimethylation in single cells, and inactivation of the H3K9 methyltransferase G9a reduces the NL contact frequencies. These results indicate that nuclear positioning and histone modification of LADs are both stochastic yet linked in single cells. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes. LaminB1-chromatin interactions were assayed in human HT1080 cells by induction of Dam_LMNB1 expression in a stable cell line with shield1.

ORGANISM(S): Homo sapiens

SUBMITTER: Bas van Steensel

PROVIDER: E-GEOD-40094 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Evolutionary conservation of nuclear lamina-genome interactions

Project description:Regulation of gene expression is highly conserved between vertebrates, yet the genomic binding patterns of transcription factors are poorly conserved, suggesting that other mechanisms may contribute. The spatial organization of chromosomes in the nucleus is known to affect gene activity, but it is unclear to what extent this organization is conserved in evolution. Genome-wide maps of nuclear lamina (NL) interactions show that human and mouse chromosomes have highly similar folding patterns inside the nucleus. Breaks in synteny are often located at transition points between NL interacting and intra-nuclear regions. Data were compared against data from Peric-Hupkes, Meuleman et al. (Molecular Cell, 2010). LaminB1-chromatin interactions were assayed in human ESCs and human HT1080 cells. LaminA-chromatin interactions were assayed in human HT1080 cells. For the all samples there were 2 biological replicates, that were hybridized in a dye-swap design.

2012-10-10 | E-GEOD-22428 | biostudies-arrayexpress

Domains of genomewide gene expression dysregulation in Down syndrome [array]

Project description:Trisomy 21 (T21) is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in T21, and to eliminate the noise of the genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for T21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either up- or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twinsM-bM-^@M-^Y fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of DS and wild-type, also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall LADs position was not altered in trisomic cells. However, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results suggest that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome and that GEDDs may therefore contribute to some T21 phenotypes. LaminB1-chromatin interactions in a pair of monozygotic twins discordant for trisomy21

2014-04-08 | E-GEOD-55289 | biostudies-arrayexpress

Stochastic genome-nuclear lamina interactions: Modulating roles of Lamin A and BAF

Project description:The nuclear lamina (NL) is a filamentous layer lining the inner-nuclear-membrane (INM) that aids in the organization of the genome in large domains of low transcriptional activity. Recently, it was shown that the single-cell genome-NL interactions are much more dynamic than previously anticipated, which challenges the concept of the NL as a safe guard for transcriptional repressed genes. Here we discuss the role of the NL in light of these new findings and introduce Lamin A and BAF as potential modulators of LAD positioning BAF-chromatin and Lamin B2-chromatin interactions were assayed in human HT1080 by DamID on Nimblegen microarrays, with two biological replicates each, that were hybridized in a dye-swap design.

2014-02-15 | E-GEOD-55066 | biostudies-arrayexpress

Stochastic genome - nuclear lamina contacts are linked to histone H3K9 dimethylation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-01-31 | E-GEOD-40112 | biostudies-arrayexpress

Reorganization of nuclear lamina – genome interactions upon differentiation of embryonic stem cells.

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2010-05-27 | E-GEOD-17051 | biostudies-arrayexpress

Domains of genomewide gene expression dysregulation in Down syndrome

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2014-04-08 | E-GEOD-55426 | biostudies-arrayexpress

The insulator protein SU(HW) modulates nuclear lamina interactions of the Drosophila genome: DamID

Project description:Specific interactions of the genome with the nuclear lamina (NL) are thought to assist chromosome folding inside the nucleus and to contribute to the regulation of gene expression. High-resolution mapping has recently identified hundreds of large, sharply defined lamina-associated domains (LADs) in the human genome, and suggested that the insulator protein CTCF may help to demarcate these domains. Here, we report the detailed structure of LADs in Drosophila cells, and investigate the putative roles of five insulator proteins in LAD organization. We found that of these five proteins, only SU(HW) binds preferentially at LAD borders and at specific positions inside LADs, while GAF, CTCF, BEAF-32 and DWG are mostly absent from these regions. By knockdown and overexpression studies we demonstrate that SU(HW) weakens LAD – NL interactions by a local antagonistic effect. Our results provide insights into the evolution of LAD organization and reveal a role for SU(HW) in the regulation of genome – NL interactions. DamID experiments for Lamin, CTCF, SU(HW), GAF, DWG, and BEAF-32, and for Lamin after overexpression and after knockdown of SU(HW), were performed in Drosophila cell cultures. Samples were hybridized to 380k NimbleGen arrays with 300 bp probe spacing. Every experiment was done in duplicate in the reverse dye orientation. The supplementary file 'GSE20311_DamID_norm_mean.txt' contains the mean log2(Dam-fusion/Dam-only) values of two replicates.

2011-01-24 | E-GEOD-20311 | biostudies-arrayexpress

Stochastic genome - nuclear lamina contacts are linked to histone H3K9 dimethylation (RNA-seq data)

Project description:The nuclear lamina (NL) interacts with hundreds of large genomic regions termed lamina-associated domains (LADs). The dynamics of these interactions and the relation to epigenetic modifications are poorly understood. We visualized the fate of LADs in single cells using a novel 'molecular contact memory' approach. In each interphase nucleus, only ~30% of LADs are positioned at the periphery; these LADs are in intermittent molecular contact with the NL but remain constrained to the periphery. Upon mitosis, LAD positioning is not detectably inherited but instead is stochastically reshuffled. Contact of individual LADs with the NL correlates with their degree of H3K9 dimethylation in single cells, and inactivation of the H3K9 methyltransferase G9a reduces the NL contact frequencies. These results indicate that nuclear positioning and histone modification of LADs are both stochastic yet linked in single cells. Collectively, these results highlight principles of the dynamic spatial architecture of chromosomes. 12 RNA-seq experiments for 6 samples, each with a biological replicate: m6ATracer-VP16+/DamLaminB1+ m6ATracer-VP16+/DamLaminB1- m6ATracer-VP16-/DamLaminB1- m6ATracer-GFP+/DamLaminB1+ m6ATracer-GFP+/DamLaminB1- m6ATracer-GFP-/DamLaminB1-

2013-01-31 | E-GEOD-40111 | biostudies-arrayexpress

Genome-wide maps of nuclear lamina interactions in single human cells (CEL-seq)

Project description:Mammalian interphase chromosomes interact with the nuclear lamina (NL) through hundreds of large Lamina Associated Domains (LADs). We report a method to map NL contacts genome-wide in single human cells. Analysis of ~400 maps reveals a core architecture of gene-poor LADs that contact the NL with high cell-to-cell consistency, interspersed by LADs with more variable NL interactions. The variable contacts are more sensitive to a change in genome ploidy than the consistent contacts. Single-cell maps indicate that NL contacts involve multivalent interactions over hundreds of kilobases. Moreover, we observe extensive intra-chromosomal coordination of NL contacts, even over tens of megabases. Such coordinated loci exhibit preferential interactions as detected by Hi-C. Finally, single-cell gene expression and chromatin accessibility analysis shows that loci with consistent NL contacts are expressed at lower levels and are more consistently inaccessible than loci with lower contact frequencies. These results highlight fundamental principles of single cell chromatin organization. In this dataset, single-cell mRNA sequencing results from 96 single KBM7 cells have been deposited

2015-09-24 | E-GEOD-68596 | biostudies-arrayexpress

DamID of Dam::LMN-1 and Dam::EMR-1 in Caenorhabditis elegans adult worms

Project description:Laminopathies are caused by mutations in components of the nuclear envelope (NE). While most NE components are widely expressed, laminopathies affect only a subset of tissues. However, the understanding of the molecular mechanisms that explain this phenomenon is still elusive. Here we have performed a genome wide DamID analysis in adult C. elegans nematodes comparing the DNA association profile of two components of the NE, Lamin/LMN-1 and Emerin/EMR-1. Although both proteins were associated to silent DNA, EMR-1 showed a predominant role in the anchoring of muscle and neuronal promoters to the nuclear periphery. Deletion of either EMR-1 or LEM-2, another integral NE protein, caused local changes in nuclear architecture with both increased and decreased LMN-1 association. Comparison of Dam::LMN-1 and Dam::EMR-1 DNA assotiation in wild type strains and Dam::LMN-1 DNA association in wild type, lem-2(tm1582) and emr-1(gk119) mutant backgrounds.

2013-12-02 | E-GEOD-44188 | biostudies-arrayexpress

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