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Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

ABSTRACT: Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

PROVIDER: PRJNA511977 | ENA |

REPOSITORIES: ENA

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Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

Project description:Background: The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Results: Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to chromatin redistribution and decompaction. Consequently, lamina-associated domains (LADs) are detached from the nuclear periphery. The inter-chromosomal interactions and overlap between chromosome territories are increased. Moreover, Hi-C data revealed that lamin B1 is required for the integrity and segregation of chromatin compartments but not for the topologically associating domains (TADs). Using live cell single molecule tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Conclusions: Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting its crucial role in chromatin higher-order structure and chromatin dynamics.

2020-11-08 | GSE124409 | GEO

Lamin B1 ChIPseq experiments from ER:RAS IMR90s

Project description:Lamin B1 from OIS IMR90s We used ChIP-seq to examine the global binding of Lamin B1 in human IMR90 oncogene-induced senescence

2014-12-15 | E-GEOD-53331 | biostudies-arrayexpress

Lamin B1 regulates somatic mutations and progression of B cell malignancies

Project description:Somatic hypermutation (SHM) is a pivotal process in adaptive immunity that occurs in the germinal centre and allows B-cells to change their primary DNA sequence and diversify their antigen receptors. Here, we report that genome binding of Lamin B1, a component of the nuclear envelope involved in epigenetic chromatin regulation, is reduced during B cell activation and formation of lymphoid germinal centres. ChIP-Seq analysis showed that kappa and heavy variable immunoglobulin domains were released from the Lamin B1 suppressive environment when SHM was induced in B cells. RNAi-mediated reduction of Lamin B1 resulted in spontaneous SHM as well as kappa-light chain aberrant surface expression. Finally, Lamin B1 expression level was directly proportional to 5-year survival rate in chronic lymphocytic leukaemia, and was strongly involved in transformation of follicular lymphoma. In summary, here we report that Lamin B1 is a negative epigenetic regulator of SHM in normal B-cells and a "mutational gatekeeper", suppressing the aberrant mutations that drive lymphoid malignancy.

2017-08-03 | GSE89869 | GEO

Lamin B1 dependent transcriptional control in neural progenitor cells

Project description:Through knocking out Lamin B1, we found that lamin B1 regulets hundreds of genes in neural progenitor cells, which underlie differentiation of neural protenitor cells

2021-02-10 | GSE156156 | GEO

Lamin B1 overexpression alters chromatin organization and gene expression (mRNA-seq)

Project description:Overexpression of Lamin B1 leads to the redistribution of H3K9me3 heterochromatin away from the nuclear periphery and into heterochromatic DNA foci within the nucleoplasm. These changes in chromatin organization correlate with misregulated gene expression (mRNA-sequencing), but do not correlate with altered H3K9me3 deposition across the genome (Cut&Run).

2023-04-23 | GSE212107 | GEO

Huntington’s disease as a lamin B1 nuclear envelopathy

Project description:Lamins, the major structural proteins within the nuclear lamina, are crucial for the functionality of cellular nucleus and their alterations are involved in the so-called laminopathies. We previously found that Huntington’s disease (HD), a hereditary neurodegenerative disorder caused by an expansion of a CAG repeat in the huntingtin (htt) gene, courses with increased lamin B protein levels in specific brain regions in both mouse models and patients. We now show that these changes are mostly restricted to lamin B1, occur in striatal medium-sized spiny neurons and CA1 hippocampal neurons, and are accompanied by altered nuclear morphology, nucleocytoplasmic transport disruption and un-structuring of lamin-associated chromatin domains. Normalization of lamin B1 levels by betulinic acid administration in the R6/1 mouse model of HD results in beneficial restoring of nuclear lamina homeostasis and prevention of motor and cognitive dysfunction, opening a window for a new therapeutic approach for HD and other B1-type laminophaties.

2020-11-10 | GSE139884 | GEO

Expression data from functional studies using RNAi on Lamin B1 in BL2 cells

Project description:Lamin B1 is a component of the nuclear envelope involved in epigenetic chromatin regulation and is reduced during B cell activation and formation of lymphoid germinal centres. RNAi-mediated reduction of Lamin B1 results in spontaneous SHM as well as kappa-light chain aberrant surface expression showing that Lamin B1 is a negative epigenetic regulator of SHM. We used Affymetrix Exon 1.0 ST microarrays to detail the global programme of gene expression underlying changes induced in siRNA-treated Lamin B1low BL2 cells. siRNA-mediated reduction of nuclear Lamin B1 incorporation resulted in a general upregulation of positive cell cycle regulatory genes which in turn occurred alongside an upregulation of genes responsible for cell cycle checkpoint execution or cell cycle arrest, and were specific for LMNB1 reduction.

2017-08-16 | GSE98529 | GEO

Lamin B1 overexpression alters chromatin organization and gene expression (Cut&Run-seq)

2023-04-23 | GSE212108 | GEO

Lamin B1 ChIPseq experiments from ER:RAS IMR90s

Project description:Lamin B1 from OIS IMR90s

2014-12-15 | GSE53331 | GEO

Human lamin B1: stress-induced phosphorylation

Project description:This is a small scale study of the phosphorylation state of human lamin B1 immunoprecipitated from control cells or cells treated with methyl methane sulphonate (MMS, acting as a DNA damage stressor agent)

2017-05-30 | PXD006459 | Pride

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