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

Chao, Lei; Li, Mengfan; Shao, Shuang; Li, Chen; Ai, Shanshan; Bai, Xue; Hou, Yingping; Zhang, Yiwen; Li, Ruifeng; Fan, Xiaoying; He, Aibin; Li, Cheng; Sun, Yujie

doi:10.1007/s13238-020-00794-8

Cited by 60 publications

(62 citation statements)

References 105 publications

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“…In addition, knockout of lamin could result in the dislocation of heterochromatin [ 45 , 46 ]. Recent experimental studies proposed that the competition between the lamin B1, which tethers heterochromatin to the nuclear periphery, and the nuclear matrix, which pulls the heterochromatin to the nuclear interior, regulates the 3D chromatin structure [ 47 ], which is also consistent with our simulation results. Such an effect of lamin was also investigated in some recent simulation studies [ 3 , 33 , 34 ].…”

Section: Discussionsupporting

confidence: 91%

A DNA Sequence Based Polymer Model for Chromatin Folding

Zhou

Gao

2021

IJMS

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The recent development of sequencing technology and imaging methods has provided an unprecedented understanding of the inter-phase chromatin folding in mammalian nuclei. It was found that chromatin folds into topological-associated domains (TADs) of hundreds of kilo base pairs (kbps), and is further divided into spatially segregated compartments (A and B). The compartment B tends to be located near to the periphery or the nuclear center and interacts with other domains of compartments B, while compartment A tends to be located between compartment B and interacts inside the domains. These spatial domains are found to highly correlate with the mosaic CpG island (CGI) density. High CGI density corresponds to compartments A and small TADs, and vice versa. The variation of contact probability as a function of sequential distance roughly follows a power-law decay. Different chromosomes tend to segregate to occupy different chromosome territories. A model that can integrate these properties at multiple length scales and match many aspects is highly desired. Here, we report a DNA-sequence based coarse-grained block copolymer model that considers different interactions between blocks of different CGI density, interactions of TAD formation, as well as interactions between chromatin and the nuclear envelope. This model captures the various single-chromosome properties and partially reproduces the formation of chromosome territories.

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Section: Discussionsupporting

confidence: 91%

A DNA Sequence Based Polymer Model for Chromatin Folding

Zhou

Gao

2021

IJMS

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“…Nonetheless, in our view, the negative ChIP-seq results are in favor of a hypothesis that MpNMCP is not involved in organizing genome folding at the nuclear periphery like the Arabidopsis CRWN1. This notion is supported by our Hi-C data that there was no increase of interchromosomal contacts in Mpnmcp mutant nuclei (Figure 6B and Supplementary Figure 6), which were otherwise observed in mutants having deficiency in perinuclear chromatin tethering (Hu et al, 2019;Chang et al, 2020). Nevertheless, it is clear that MpNMCP is required for proper chromatin organization, at least for the repeat region at the V chromosome, since it detached from the nuclear periphery and became decondensed in Mpnmcp mutants (Figure 5).…”

Section: Mpnmcp Indirectly Regulates Perinuclear Location Of Chromatinsupporting

confidence: 67%

Characterization of a Plant Nuclear Matrix Constituent Protein in Liverwort

et al. 2021

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The nuclear lamina (NL) is a complex network of nuclear lamins and lamina-associated nuclear membrane proteins, which scaffold the nucleus to maintain structural integrity. In animals, type V intermediate filaments are the main constituents of NL. Plant genomes do not encode any homologs of these intermediate filaments, yet plant nuclei contain lamina-like structures that are present in their nuclei. In Arabidopsis thaliana, CROWDED NUCLEI (CRWN), which are required for maintaining structural integrity of the nucleus and specific perinuclear chromatin anchoring, are strong candidates for plant lamin proteins. Recent studies revealed additional roles of Arabidopsis Nuclear Matrix Constituent Proteins (NMCPs) in modulating plants’ response to pathogen and abiotic stresses. However, detailed analyses of Arabidopsis NMCP activities are challenging due to the presence of multiple homologs and their functional redundancy. In this study, we investigated the sole NMCP gene in the liverwort Marchantia polymorpha (MpNMCP). We found that MpNMCP proteins preferentially were localized to the nuclear periphery. Using CRISPR/Cas9 techniques, we generated an MpNMCP loss-of-function mutant, which displayed reduced growth rate and curly thallus lobes. At an organelle level, MpNMCP mutants did not show any alteration in nuclear morphology. Transcriptome analyses indicated that MpNMCP was involved in regulating biotic and abiotic stress responses. Additionally, a highly repetitive genomic region on the male sex chromosome, which was preferentially tethered at the nuclear periphery in wild-type thalli, decondensed in the MpNMCP mutants and located in the nuclear interior. This perinuclear chromatin anchoring, however, was not directly controlled by MpNMCP. Altogether, our results unveiled that NMCP in plants have conserved functions in modulating stress responses.

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“…36,[40][41][42][43][44] Although laminassociated domains (LADs) contribute to a basal chromosome architecture, a large body of work has demonstrated a secondary role for lamina scaffolding in compartmental segregation of heterochromatin and euchromatin. [31][32][33][34][35][45][46][47][48][49] In vitro assembled nucleosomal arrays harboring histone H3 lysine 9 di-and trimethylation (H3K9me2 and H3K9me3) marks undergo phase separation with heterochromatin protein 1 (HP1) and associated proteins to form macromolecule-enriched liquid droplets, reminiscent of heterochromatin. 38 However, the role of histone modifications in regulating compartmentalization in vivo remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome

Chang

et al. 2021

Cell Res

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134

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Organization of the genome into euchromatin and heterochromatin appears to be evolutionarily conserved and relatively stable during lineage differentiation. In an effort to unravel the basic principle underlying genome folding, here we focus on the genome itself and report a fundamental role for L1 (LINE1 or LINE-1) and B1/Alu retrotransposons, the most abundant subclasses of repetitive sequences, in chromatin compartmentalization. We find that homotypic clustering of L1 and B1/Alu demarcates the genome into grossly exclusive domains, and characterizes and predicts Hi-C compartments. Spatial segregation of L1-rich sequences in the nuclear and nucleolar peripheries and B1/Alu-rich sequences in the nuclear interior is conserved in mouse and human cells and occurs dynamically during the cell cycle. In addition, de novo establishment of L1 and B1 nuclear segregation is coincident with the formation of higher-order chromatin structures during early embryogenesis and appears to be critically regulated by L1 and B1 transcripts. Importantly, depletion of L1 transcripts in embryonic stem cells drastically weakens homotypic repeat contacts and compartmental strength, and disrupts the nuclear segregation of L1- or B1-rich chromosomal sequences at genome-wide and individual sites. Mechanistically, nuclear co-localization and liquid droplet formation of L1 repeat DNA and RNA with heterochromatin protein HP1α suggest a phase-separation mechanism by which L1 promotes heterochromatin compartmentalization. Taken together, we propose a genetically encoded model in which L1 and B1/Alu repeats blueprint chromatin macrostructure. Our model explains the robustness of genome folding into a common conserved core, on which dynamic gene regulation is overlaid across cells.

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

Cited by 60 publications

References 105 publications

A DNA Sequence Based Polymer Model for Chromatin Folding

A DNA Sequence Based Polymer Model for Chromatin Folding

Characterization of a Plant Nuclear Matrix Constituent Protein in Liverwort

Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome

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