Lamina Associated Domains dependent of chromatin state and A-type lamins
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA380656 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Three-dimensional (3D) genome organization is thought to be important for regulation of gene expression. Chromosome conformation capture-based studies have uncovered ensemble organizational principles such as active (A) and inactive (B) compartmentalization. In addition, large inactive regions of the genome associate with the nuclear lamina, the Lamina Associated Domains (LADs). Here we investigate the dynamic relationship between A/B-compartment organization and the 3D organization of LADs. Using refined algorithms to identify active (A) and inactive (B) compartments from Hi-C data and to define LADs from DamID, we confirm that the LADs correspond to the B-compartment. Using specialized chromosome conformation paints, we show that LAD and A/B-compartment organization are dependent upon chromatin state and A-type lamins. By integrating single-cell Hi-C data with live cell imaging and chromosome conformation paints, we demonstrate that self-organization of the B-compartment within a chromosome is an early event post-mitosis and occurs prior to organization of these domains to the nuclear lamina.
2020-03-27 | GSE124205 | GEO
Project description:Three-dimensional (3D) genome organization is thought to be important for regulation of gene expression. Chromosome conformation capture-based studies have uncovered ensemble organizational principles such as active (A) and inactive (B) compartmentalization. In addition, large inactive regions of the genome associate with the nuclear lamina, the Lamina Associated Domains (LADs). Here we investigate the dynamic relationship between A/B-compartment organization and the 3D organization of LADs. Using refined algorithms to identify active (A) and inactive (B) compartments from Hi-C data and to define LADs from DamID, we confirm that the LADs correspond to the B-compartment. Using specialized chromosome conformation paints, we show that LAD and A/B-compartment organization are dependent upon chromatin state and A-type lamins. By integrating single-cell Hi-C data with live cell imaging and chromosome conformation paints, we demonstrate that self-organization of the B-compartment within a chromosome is an early event post-mitosis and occurs prior to organization of these domains to the nuclear lamina.
2020-03-27 | GSE97092 | GEO
Project description:The nuclear lamina interacts with the genome through megabase-size lamina-associated domains (LADs). LADs have been identified in proximity labeling assays and recently by chromatin immunoprecipitation-sequencing (ChIP-seq) of A- and B-type lamins. LADs localize mainly to the nuclear periphery, they are gene-poor and largely heterochromatic. Here, we show that the mode of chromatin fragmentation for ChIP, namely either bath sonication (used to date for ChIP of nuclear lamins) or digestion with micrococcal nuclease (MNase) leads to the discovery of distinct sets of lamin-interacting domains (which we refer to as LiDs) with distinct gene content, histone composition enrichment and relationship to lamin B1-interacting domains. We find that total genome coverage by lamin A/C ('LMNA') LiDs identified in sonicated or MNase-digested chromatin is similar (~730 megabases). Over half of these domains, however, are uniquely detected in sonicated or MNase-digested chromatin. Whereas sonication-specific LMNA LiDs are gene-poor and devoid of a broad panel of histone modifications, MNase-specific LMNA LiDs are of higher gene density and are enriched in H3K9me3, H3K27me3 and in histone variant H2A.Z. Analysis of published LMNB1 LADs and of LMNB1 LiDs identified by ChIP-seq further shows that LMNA can associate with 'open' chromatin domains displaying euchromatin features which are not associated with LMNB1. The differential genetic and epigenetic properties of lamin-interacting chromatin domains indicate the existence of distinct LiD populations identifiable in different chromatin contexts, including nuclease-accessible 'open' regions presumably localized in the nuclear interior.
2015-03-24 | GSE57149 | GEO
Project description:The nuclear lamina is a proteinaceous network of filaments that provide both structural and gene regulatory functions by tethering proteins and large domains of DNA, so-called lamin associated domains (LADs), to the periphery of the nucleus. LADs are a large fraction of the mammalian genome that are repressed, in part, by their association to the nuclear periphery. The genesis and maintenance of LADs is poorly understood as are the proteins that participate in these functions. In an effort to identify proteins that reside at the nuclear periphery and potentially interact with LADs, we have taken a two-pronged approach. First, we have undertaken an interactome analysis of the inner nuclear membrane bound LAP2β to further characterize the nuclear lamina proteome. To accomplish this, we have leveraged the BioID system, which previously has been successfully used to characterize the nuclear lamina proteome. Second, we have established a system to identify proteins that bind to LADs by developing a chromatin directed BioID system. We combined the BioID system with the m6A-tracer system which binds to LADs in live cells to identify LAD proximal and nuclear lamina proteins. In combining these datasets, we have further characterized the protein network at the nuclear lamina as well as identified putative LAD proximal proteins. Our analysis identifies many heterochromatin related proteins related to H3K9 methylation processes as well as many proteins related to cell cycle regulation identifying important proteins essential for LAD function.
2021-03-09 | PXD012943 | Pride
Project description:The nuclear lamina provides a repressive chromatin environment at the nuclear periphery. However, whereas most genes in lamina-associated domains (LADs) are repressed, approximately ten percent reside in local euchromatic contexts and are expressed. How these genes are regulated and whether they are able to contact regulatory elements in LADs or outside LADs remains unclear. Here, we integrate transcriptomic, chromatin states, microscopy and publicly available enhancer-capture Hi-C data to show that expressed genes in LADs are able to connect to enhancers in LADs and inter-LADs. Our data favor a model where the spatial topology of chromatin at the nuclear lamina is compatible with transcriptional regulation in this dynamic nuclear compartment.
2023-01-01 | GSE221288 | GEO
Project description:Lamins are components of the peripheral nuclear lamina and interact with heterochromatic genomic regions, termed lamina-associated domains (LADs). In contrast to lamin B1, lamin A/C also localizes throughout the nucleus, where it associates with the chromatin-binding protein lamina-associated polypeptide (LAP) 2alpha. Here we show lamin A/C also interacts with euchromatin, as determined by chromatin immunoprecipitation analyses of eu- and heterochromatin-enriched samples. By way of contrast, lamin B1 was only found associated with heterochromatin. Euchromatic regions occupied by lamin A/C overlap with those bound by LAP2alpha, the depletion of which shifts binding of lamin A/C towards more heterochromatic regions. These alterations in lamin A/C chromatin interaction affect epigenetic histone marks in euchromatin without significantly affecting gene expression, while loss of lamin A/C in heterochromatic regions increased gene expression. Our data show a novel role of nucleoplasmic lamin A/C and LAP2alpha in regulating euchromatin. Examination of LaminA, LaminB and Lap2a DNA binding in Lap2alpha +/+ and Lap2a -/- cells and according changes in Histone modifications and gene expression
2016-01-19 | E-GEOD-70148 | biostudies-arrayexpress
Project description:Lamins are components of the peripheral nuclear lamina and interact with heterochromatic genomic regions, termed lamina-associated domains (LADs). In contrast to Lamin B11, lamin A/C also localizes throughout the nucleus, where it associates with the chromatin-binding protein lamina-associated polypeptide (LAP) 2alpha. Here we show lamin A/C also interacts with euchromatin, as determined by chromatin immunoprecipitation analyses of eu- and heterochromatin-enriched samples. By way of contrast, Lamin B11 was only found associated with heterochromatin. Euchromatic regions occupied by lamin A/C overlap with those bound by LAP2alpha, the depletion of which shifts binding of lamin A/C towards more heterochromatic regions. These alterations in lamin A/C chromatin interaction affect epigenetic histone marks in euchromatin without significantly affecting gene expression, while loss of lamin A/C in heterochromatic regions increased gene expression. Our data show a novel role of nucleoplasmic lamin A/C and LAP2alpha in regulating euchromatin. Examination of Lamin A/C, Lamin B1 and Lap2a DNA binding in Lap2alpha +/+ and Lap2a -/- cells and according changes in Histone modifications and gene expression
2016-01-19 | E-GEOD-70147 | biostudies-arrayexpress
Project description:In mammals, the nuclear lamina interacts with hundreds of large genomic regions, termed lamina-associated domains (LADs) that are generally in a transcriptionally repressed state. Lamins form the major structural component of the lamina and have been reported to bind DNA and chromatin. Here we systematically evaluated whether lamins are necessary for the peripheral localization of LADs in murine embryonic stem cells. Surprisingly, removal of essentially all lamins did not have any detectable effect on the genome-wide interaction pattern of chromatin with the inner nuclear membrane. This suggests that other components of the inner nuclear membrane mediate these interactions. 2 samples, each with a biological replicate: wt mESC, B type lamin null (dKO) dKO mESC
2015-03-10 | E-GEOD-62684 | biostudies-arrayexpress
Project description:Purpose: To compare the effects on Lamina Associated Domains (LADs) of shRNA treatment against lamin isotypes. Results: Using an optimized data analysis workflow (LADetector, available at https://github.com/thereddylab/LADetector), We found near identical sequences within the genome-wide maps indicating that ensemble methods are not effective for measuring random perturbations - perturbations that vary from cell to cell.
2020-07-07 | GSE153919 | GEO
Project description:Lamins are components of the peripheral nuclear lamina and interact with heterochromatic genomic regions, termed lamina-associated domains (LADs). In contrast to lamin B1, lamin A/C also localizes throughout the nucleus, where it associates with the chromatin-binding protein lamina-associated polypeptide (LAP) 2alpha. Here we show lamin A/C also interacts with euchromatin, as determined by chromatin immunoprecipitation analyses of eu- and heterochromatin-enriched samples. By way of contrast, lamin B1 was only found associated with heterochromatin. Euchromatic regions occupied by lamin A/C overlap with those bound by LAP2alpha, the depletion of which shifts binding of lamin A/C towards more heterochromatic regions. These alterations in lamin A/C chromatin interaction affect epigenetic histone marks in euchromatin without significantly affecting gene expression, while loss of lamin A/C in heterochromatic regions increased gene expression. Our data show a novel role of nucleoplasmic lamin A/C and LAP2alpha in regulating euchromatin.
2016-01-19 | GSE70148 | GEO