The nuclear lamina maintains global spatial organization of chromatin in Drosophila
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ABSTRACT:
PROVIDER: PRJNA432720 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6667396_1.fastq.gz | Fastqsanger.gz | |||
| SRR6667396_2.fastq.gz | Fastqsanger.gz | |||
| SRR6667397_1.fastq.gz | Fastqsanger.gz | |||
| SRR6667397_2.fastq.gz | Fastqsanger.gz | |||
| SRR6667398_1.fastq.gz | Fastqsanger.gz |
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Project description:The nuclear lamina (NL) is a meshwork of lamins and lamin-associated proteins lining the nuclear envelope (NE). Chromatin adjoining the NL in lamina-associated domains (LADs) is densely packed and contains predominantly silent genes. However, how the NL impacts on global chromatin architecture is poorly understood. Here, we show that NL disruption in Drosophila S2 cells leads to bulk chromatin compactization and repositioning from the NE. This increases the chromatin density in the topologically-associating domains (TADs) harboring active genes, and enhances inter-TAD interactions resulting in the intermingling of active and inactive compartments. Importantly, upon NL disruption, a fraction of TADs strongly overlapping with LADs becomes less compact, whilst resident genes are derepressed. Two-color FISH confirms that a a TAD is more decompacted following its release from the NL. Finally, polymer simulations show that chromatin binding to the NL can per se compact attached TADs. Collectively, our findings demonstrate a dual function of the NL in shaping the 3D genome. Attachment of TADs to the NL makes them more condensed but decreases the overall chromatin density in the nucleus by stretching interphase chromosomes.
2019-02-08 | GSE110082 | GEO
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
Project description:The nuclear lamina (NL) plays various roles and participates in nuclear integrity, chromatin organization, and transcriptional regulation. Lamin proteins, the main components of the NL, form a homogeneous meshwork structure under the nuclear envelope. Lamins are essential, but it is unknown whether their homogeneous distribution is important for nuclear function. Here, we found that PIGB, an enzyme involved in glycosylphosphatidylinositol (GPI) synthesis, is responsible for the homogeneous lamin meshwork in Drosophila. Loss of PIGB resulted in heterogeneous distributions of B-type lamin and lamin-binding proteins in larval muscles. These phenotypes were rescued by expression of PIGB lacking GPI synthesis activity. The PIGB mutant exhibited changes in lamina-associated domains that are large heterochromatic genomic regions in the NL, reduction of nuclear stiffness, and deformation of muscle fibers. These results suggest that PIGB maintains the homogeneous meshwork of the NL, which may be essential for chromatin distribution and nuclear mechanical properties.
| S-EPMC10808031 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE41751: Correlated alterations in genome organization, histone methylation, and DNA-lamina interactions in Hutchinson-Gilford progeria syndrome (expression) GSE41757: Correlated alterations in genome organization, histone methylation, and DNA-lamina interactions in Hutchinson-Gilford progeria syndrome (ChIP-seq) GSE41763: Correlated alterations in genome organization, histone methylation, and DNA-lamina interactions in Hutchinson-Gilford progeria syndrome (Hi-C) Refer to individual Series
2012-10-30 | E-GEOD-41764 | biostudies-arrayexpress
Project description:Models of nuclear genome organization often propose a binary division into active versus inactive compartments yet typically overlook nuclear bodies. Here we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nuclear locales: the nuclear lamina, nuclear speckles, and nucleoli. Whereas gene expression correlates mostly with nuclear speckle proximity, DNA replication timing correlates with proximity to multiple nuclear locales. Speckle attachment regions emerge as DNA replication initiation zones whose replication timing and gene composition vary with their attachment frequency. Most facultative LADs retain a partially repressed state as iLADs, despite their positioning in the nuclear interior. Knock out of two lamina proteins, Lamin A and LBR, causes a shift of H3K9me3-enriched LADs from lamina to nucleolus, and a reciprocal relocation of H3K27me3-enriched partially repressed iLADs from nucleolus to lamina. Thus, these partially repressed iLADs appear to compete with LADs for nuclear lamina attachment with consequences for replication timing. The nuclear organization in adherent cells is polarized with nuclear bodies and genomic regions segregating both radially and relative to the equatorial plane. Together, our results underscore the importance of considering genome organization relative to nuclear locales for a more complete understanding of the spatial and functional organization of the human genome.
2025-05-14 | GSE296389 | GEO
Project description:Proper genome functionality is underpinned by the non-random, spatial or ganisation of chromatin. At the periphery of the nucleus, the association of chr omatin with the nuclear lamina is thought to facilitate both structural organisa tion and regulation of gene expression. Except for a small number of individual loci, the regions of the human genome that locate at the nuclear lamina have not been identified. Here we used DamID to map the interaction sites of lamin B1 at high resolution in human fibroblasts. We show that almost half of the human gen ome preferentially associates with the nuclear lamina. Chromatin-lamina interact ions occur via sharply demarcated domains of up to several megabases in size, wh ich are bordered by similar sized domains that do not associate with the lamina. Lamina associated domains (LADs) are typified by low gene density and low gene expression levels. This is reflected by low levels of PolII binding and histone modification H3K4me2, in combination with enrichment of H3K27me3 (and H3K9?). A considerable subset of LADs is flanked by active promoters pointing outwards, or by the insulator protein CTCF, suggesting possible mechanisms of LAD confinemen t. Finally, we found that chromosome re-arrangements occur more frequently betwe en loci located either within or outside LADs. The identification of enormous, s harply defined stretches of the human genome that associate with the nuclear lam ina provides unprecedented insights into the 3D organisation of chromatin within the nucleus. Our results reveal the division of the human genome into periphera l and internal domains, which is echoed in genome functionality. Keywords: DamID
2008-05-07 | GSE8854 | GEO
Project description:Antagonism between H3K27me3 and genome-lamina association drives atypical spatial genome organization in the totipotent embryo
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Project description:The three-dimensional organization of chromosomes within the nucleus and its dynamics during differentiation are largely unknown. We present a genome-wide analysis of the interactions between chromatin and the nuclear lamina during differentiation of mouse embryonic stem cells (ESCs) into lineage-committed neural precursor cells (NPCs) and terminally differentiated astrocytes. Chromatin in each of these cell types shows a similar organization into large lamina associated domains (LADs), which represent a transcriptionally repressive environment. During sequential differentiation steps, lamina interactions are progressively modified at hundreds of genomic locations. This remodeling is typically confined to individual transcription units and involves many genes that determine cellular identity. From ESCs to NPCs, the majority of genes that move away from the lamina are concomitantly activated. Strikingly, a significant amount remain inactive yet become primed for activation by further differentiation. These results suggest that lamina-genome interactions are widely involved in the control of gene expression programs during lineage commitment and terminal differentiation. laminB1-chromatin interactions were assayed in 4 different mouse cell-types. For each cell-type there were 2 biological replicates, that were hybridized in a dye-swap design.
2010-05-27 | E-GEOD-17051 | biostudies-arrayexpress
Project description:The nuclear organization of the genome is accepted as an important feature of gene expression regulation. However, it has remained unknown what the spatial organization of a single transcribed gene is. Here, we made use of several long highly expressed mammalian genes to describe their structure and spatial arrangement during transcription. We demonstrate that an expressed gene forms a transcription loop with RNA polymerases moving along the loop and carrying nascent RNAs that undergo co-transcriptional splicing. Transcription loops dynamically modify their harboring loci and extend into the nuclear interior due to their intrinsic stiffness. We hypothesize that the stiffness of the transcription loop arises due to a dense decoration of gene-axis with multiple voluminous nascent ribonucleoprotein particles, thus creating a stiff polymer bottlebrush. and provide supporting evidence to this hypothesis. Our work suggests that transcription loop formation is a universal principle of eukaryotic gene expression.
2021-12-06 | E-MTAB-9060 | biostudies-arrayexpress
Project description:Immune responsiveness at barrier surfaces is tailored to the exposures of each tissue. In the oral mucosa, mechanisms by which a permeable epithelium coexists with diverse microbiota and maintains integrity during inflammatory pathology remain poorly understood. We compile a multi-omics spatial map of this exposed mucosal microenvironment and uncover remarkable immune zonation with organization that is preserved even during inflammatory disease. At steady state, we identify a dynamic epithelium at the tooth interface marked by a tonic inflammatory signature which is underlined by a layer of neutrophils and a zone of APC-lymphocyte aggregates. During disease, inflammatory zones expand and organize into immature tertiary lymphoid structures, suggesting local antibody production. This spatial immune organization meets the demands for continuous protection in health and expands in function and complexity during disease while preserving key elements of zonation. Our work provides insights into tissue-specific wiring of immunity at a vulnerable human mucosal barrier.
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