Lamina Associated Domains in MEFs depleted of specific lamin isotypes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE153919 | GEO | 2020/07/07
REPOSITORIES: GEO
Similar Datasets
Project description:Purpose: To compare the interaction of various proteins (in particular Lap2b and Lamin A) at the nuclear periphery with the Lamina Associated Domains (LADs) 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 LAP2β and Lamin A, and hence LaminB1, are in close proximity to all LADs, suggesting that these proteins are not involved in discriminating subsets of LADs.
2019-11-01 | GSE128239 | GEO
Project description:Lamina Associated Domains in MEFs depleted of specific lamin isotypes
| PRJNA644536 | ENA
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:Purpose: Many mammalian genes exhibit circadian expression patterns concordant with periodic binding of transcription factors, chromatin modifications and chromosomal interactions. We determined whether lamina-associated domains (LADs) display oscillatory circadian patterns of interaction with nuclear lamin B1 during hte circadian cycle, and identified any relationship to changes in gene expression patterns in oscillatory LADs or in their vinicity. Methods: To this end, we mapped LADs by chromatin immunoprecipitation-sequencing (ChIP-seq) of lamin B1 (LMNB1) (antibody ab16048, Abcam) from mouse livers colected every 6 h, for 30 h, after entrainment of the circadian clock by 24-h fasting and refeeding. Gene expression profiles were also analyzed by RNA-sequencing (RNA-seq) at the same time points. Results and Conclusions: We report periodic interactions of chromatin domains with nuclear lamin B1, suggesting rhythmic associations of fractions of the genome with the nuclear lamina. Entrainment of the circadian clock by fasting and refeeding is accompanied in mouse liver by a gain of lamin-chromatin interactions followed by oscillations in these interactions at hundreds of lamina-associated domains (LADs). A subset of these oscillations exhibit periodicity and affect one or both LAD borders or entire stand-alone LADs. Periodic LADs are however not a dominant feature of these variable LADs, as most LADs are conserved during the circadian cycle. LAD oscillations are for the most part asynchronous between the 5’ and 3’ ends of LADs. Periodic LADs also uncoupled from gene expression patterns, periodic or not, within or in vicinity of these LADs. Accordingly, periodic genes, including central clock-control genes, are located megabases away from LADs, suggesting their residence in a transcriptionally permissive environment throughout the circadian cycle. Our data suggest autonomous oscillatory associations of fractions of the genome with the nuclear lamina, providing new evidence for rhythmic spatial configurations of chromatin. However, our data also argue that periodic LADs constitute a minor fraction of variable LADs, and reflect stochasticity in variable lamin-chromatin interactions during the circadian cycle.
2019-08-20 | GSE128675 | GEO
Project description:Dynamic interactions of nuclear lamins with chromatin through so-called lamin-associated domains (LADs) contribute to spatial arrangements of the genome. Here, we provide evidence for pre-patterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified by the nutrient sensor O-linked N-acetylglucosamine (H2BGlcNAc), which we term GADs. We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving (i) a spreading of lamin A/C-chromatin interactions during the transition from progenitor cell proliferation to cell cycle arrest, and (ii) a genome-scale redistribution these interactions through a process of LAD ‘exchange’ within hours of adipogenic induction. Chromatin state modeling reveals that lamin A/C LADs can be found both in active and repressive chromatin contexts which can be influenced by cell differentiation status. De novo formation of adipogenic lamin A/C LADs occurs non-randomly on GADs, consisting of megabase-size intergenic and repressive chromatin domains. Accordingly, while pre-differentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. Moreover, release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional upregulation after adipogenic induction, and with concordant downstream elevations in H2BGlcNAc levels and O-GlcNAc cycling. Our results unveil an epigenetic pre-patterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification. Examination of LMNA and H2BGlcNAc binding in ASCs across differentiation
2015-09-04 | E-GEOD-63346 | biostudies-arrayexpress
Project description:Purpose: to qualify and quantify the rearrangement of interactions of nuclear lamins A/C and B with the genome, in relation to nuclearradial repositioning of loci and changes in gene expression, in HepG2 cells exposed to cyclosporin A. .To compare HepG2 cell line transcriptome profiling (RNA-seq) with radially positioning of the chromatin anchored at the nuclear periphery before and after CsA treatment. Methods: To this end, we mapped lamin A and lamin B lamina-associated domains (LADs) by chromatin immunoprecipitation-sequencing (ChIP-seq) of lamin A/C (antibody sc7292x, Santa Cruz Biotechnology) and lamin B1 (antibody ab16048, Abcam), respectively. HepG2 cells were either cultured under proliferative conditions (controls) or exposed for 3 days to 10 uM cyclosporin A. We also assesed the transcriptome by RNA-seq under each condition in duplicate cultures. Results: CsA elicits accumulation of pre-lamin A in HepG2 cells, raising the hypothesis of a global rearrangement of lamin-chromatin interactions. We show here the existence of overlapping and distinct lamin A and B lamina-associated domains (which we refer to as A- and B-LADs, respectively). Whereas B-LADs largely remain constitutive, CsA elicits the formation of facultative A-LADs. Re-localization of A-LADs occur mainly on preexisting B-LADs. However, LAD rearrangement does not correlate with systematic changes in gene expression within LADs. We find a reorganization of A- and B-LADs after CsA treatment, entailing distinct contributions of A- and B- type lamins. to genome organization. Indeed, classification of lamin A LADs and lamin B LADs into properties of ‘A-only’, ‘B-only’ and ‘A-B’ LADs show an overall loss of A-only LADs after CsA treatment. A- only and B-only LADs are highly dynamic with A-B LADs being more stable.The rearrangement of lamin association after CsA treatment correlates with repositioning of loci in the nuclear space with, notably, a loss of lamin B associated with a re-localization of loci towards the nuclear center and conversely, a gain of lamin B linked to a repositioning of loci towards the nuclear periphery. Predictions on radial repositioning of LADs, and of loci within, from 3D structural models of the genome were supported by fluorescence in situ hybridization (FISH) analyses. Conclusions: We show that, while they amply co-localize on well-conserved LADs, lamins A and B also interact with distinct genomic regions that can interchange (switch) between lamin A and B upon CsA treatment. We unveil distinct lamin A and B interactions with chromatin, suggesting complementary contributions to genome conformation. Our data suggest that and lamins A and B may differentially modulate genome organization.
2019-02-19 | GSE119631 | GEO
Project description:Dynamic interactions of nuclear lamins with chromatin through so-called lamin-associated domains (LADs) contribute to spatial arrangements of the genome. Here, we provide evidence for pre-patterning of differentiation-driven formation of lamin A/C LADs by domains of histone H2B modified by the nutrient sensor O-linked N-acetylglucosamine (H2BGlcNAc), which we term GADs. We demonstrate a two-step process of lamin A/C LAD formation during in vitro adipogenesis, involving (i) a spreading of lamin A/C-chromatin interactions during the transition from progenitor cell proliferation to cell cycle arrest, and (ii) a genome-scale redistribution these interactions through a process of LAD ‘exchange’ within hours of adipogenic induction. Chromatin state modeling reveals that lamin A/C LADs can be found both in active and repressive chromatin contexts which can be influenced by cell differentiation status. De novo formation of adipogenic lamin A/C LADs occurs non-randomly on GADs, consisting of megabase-size intergenic and repressive chromatin domains. Accordingly, while pre-differentiation lamin A/C LADs are gene-rich, post-differentiation LADs harbor repressive features reminiscent of lamin B1 LADs. Moreover, release of lamin A/C from genes directly involved in glycolysis concurs with their transcriptional upregulation after adipogenic induction, and with concordant downstream elevations in H2BGlcNAc levels and O-GlcNAc cycling. Our results unveil an epigenetic pre-patterning of adipogenic LADs by GADs, suggesting a coupling of developmentally regulated lamin A/C-genome interactions to a metabolically sensitive chromatin modification.
2015-09-04 | GSE63346 | GEO
Project description:To determine if LMNA R527C mutation affect the arrangement and function of LADs, we performed Lamin A ChIP-seq in wild type and mutant MSCs. Reads of Lamin A ChIP-seq in LADs were decreased in mutant cells compared with wild type. These data suggested that the binding affinity of Lamin A to LADs was reduced after R527C mutation
2021-12-07 | GSE190196 | GEO
Project description:Using ATAC seq analysis, we showed that the MEFs with a knockout of Lmna gene (i.e., missing the lamin A/C nuclear scaffolding protein) (Lmna-/- MEFs) display a striking change in chromatin accessibility landscape (peak signals that are both up and down), both within and outside lamina-associated domains (LADs); moreover, there was a clear overrepresentation of peaks with a gain in chromatin accessibility (within and outside LADs) in the Lmna-/- MEFs, and within LADs compared to outside LADs.
2022-08-31 | GSE186677 | GEO
Project description:Interactions of chromatin with the nuclear lamina via lamina-associated domains (LADs) confers structural stability to the genome. The dynamics of positioning of LADs during differentiation, and how LADs impinge on developmental gene expression, remains elusive, however. We examined changes in the association of lamin B1 with the genome in the first 72 hours of differentiation of adipose stem cells into adipocytes. We demonstrate a repositioning of entire stand-alone LADs and of LAD edges as a prominent nuclear structural feature of early adipogenesis. Whereas adipogenic genes are released from LADs, LADs sequester downregulated or repressed genes irrelevant for the adipose lineage. However, LAD repositioning only partly concurs with gene expression changes. Differentially expressed genes in LADs, including LADs conserved throughout differentiation, reside in local euchromatic and lamin-depleted sub-domains. In these sub-domains, pre-differentiation histone modification profiles correlate with the LAD versus inter-LAD outcome of these genes during adipogenic commitment. In addition, differentially expressed genes in LADs are linked to short-range enhancers which overall co-partition with these genes in LADs versus inter-LADs during differentiation. We conclude that LADs are predictable structural features of adipose nuclear architecture that restrain non-adipogenic genes in a repressive environment.
2022-03-21 | GSE185066 | GEO