Lamina-associated domains: peripheral matters and internal affairs

Briand, Nolwenn; Collas, Philippe

doi:10.1186/s13059-020-02003-5

Cited by 203 publications

(234 citation statements)

References 159 publications

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“…Taken together, our results demonstrate that elevated lamin C levels in the fully differentiated larva muscle caused detachment of chromatin from the lamina and loss of peripheral organization, in agreement with previous studies demonstrating that both up and down regulation of lamin C levels lead to disrupted 3D chromatin organization, accompanied by reduction in repressive marks 14,18 . Furthermore, the observed central chromatin in the live lamin C OE further supports the ability of our imaging setup to detect chromatin in the interior of the nucleus, when it is indeed present.…”

Section: Lamin C Over-expression Disrupts Chromatin Localization At Tsupporting

confidence: 92%

“…The nuclear lamina controls radial chromatin organization by its dynamic tethering of chromatin to the nuclear periphery through LADs 13,14 . Since the nucleus is thought to be a mechanosensitive organelle [56][57][58] , in which the close proximity of the chromatin to the nuclear lamina might sensitize the chromatin to both mechanical inputs, as well as to changes in the nuclear lamina composition, a peripheral chromatin organization might couple between mechanical inputs and transcriptional regulation.…”

Section: Discussionmentioning

confidence: 99%

“…Consistently, genome-wide DamID analysis performed with lamin B or lamin A in culture conditions identified LADs mostly as gene poor and transcriptionally silenced sequences 12 . Specifically, variations in lamin A/C levels, induced by either its up-or down regulation, or as observed in laminopathy-associated mutations in lamin A/C, drive heterochromatin detachment from the nuclear lamina 13,14 . This was accompanied by chromatin de-condensation and reduced levels of HP1 and H3K9me3 repressive marks in mammals 15,16 , C. elegans 17 as well as in Drosophila cells 18,19 .…”

Section: Introductionmentioning

confidence: 99%

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Live imaging of chromatin distribution in muscle nuclei reveals novel principles of nuclear architecture and chromatin compartmentalization

Pavlov¹,

Lorber²,

Bajpai³

et al. 2020

Preprint

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Packaging of the chromatin within the nucleus serves as an important factor in the regulation of transcriptional output. However, information on chromatin architecture on nuclear scale in fully differentiated cells, under physiological conditions and in live organisms, is largely unavailable. Here, we imaged nuclei and chromatin in muscle fibers of live, intact Drosophila larvae. In contrast to the common view that chromatin is distributed throughout the nuclear volume, we show that the entire chromatin, including active and repressed regions, forms a peripheral layer underneath the nuclear lamina, leaving a chromatin-devoid compartment at the nucleus center. Importantly, visualization of nuclear compartmentalization required imaging of un-fixed nuclei embedded within their intrinsic tissue environment, with preserved nuclear volume. Upon fixation of similar muscle nuclei, we observed an average of three-fold reduction in nuclear volume caused by dehydration and evidenced by nuclear flattening. In these conditions, the peripheral chromatin layer was not detected anymore, demonstrating the importance of preserving native biophysical tissue environment. We further show that nuclear compartmentalization is sensitive to the levels of lamin C, since over-expression of lamin C-GFP in muscle nuclei resulted in detachment of the peripheral chromatin layer from the lamina and its collapse into the nuclear center. Computer simulations of chromatin distribution recapitulated the peripheral chromatin organization observed experimentally, when binding of lamina associated domains (LADs) was incorporated with chromatin selfattractive interactions. Reducing the number of LADs led to collapse of the chromatin, similarly to our observations following lamin C over-expression. Taken together, our findings reveal a novel mode of mesoscale organization of chromatin within the nucleus in a live organism, in which the chromatin forms a peripheral layer separated from the nuclear interior.This architecture may be essential for robust transcriptional regulation in fully differentiated cells.

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Section: Lamin C Over-expression Disrupts Chromatin Localization At Tsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Live imaging of chromatin distribution in muscle nuclei reveals novel principles of nuclear architecture and chromatin compartmentalization

Pavlov¹,

Lorber²,

Bajpai³

et al. 2020

Preprint

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“…Lamins form helical dimers that interact with each other in a head-to-tail orientation assembling into a protein meshwork. Current models of nuclear organization suggest that nuclear lamina is important for the maintenance and functioning of the 3D chromosome architecture by interacting with both the nuclear membrane and chromatin [4][5][6][7][8]. However, the precise players and mechanisms of these interactions are unknown.…”

Section: Introductionmentioning

confidence: 99%

Reorganization of the nuclear architecture in the Drosophila melanogaster Lamin B mutant lacking the CaaX box

Bondarenko

Sharakhov

2020

Nucleus

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Lamins interact with the nuclear membrane and chromatin but the precise players and mechanisms of these interactions are unknown. Here, we tested whether the removal of the CaaX motif from Lamin B disrupts its attachment to the nuclear membrane and affects chromatin distribution. We used Drosophila melanogaster Lam A25 homozygous mutants that lack the CaaX box. We found that the mutant Lamin B was not confined to the nuclear periphery but was distributed throughout the nuclear interior, colocalizing with chromosomes in salivary gland and proventriculus. The peripheral position of Lamin C, nuclear pore complex (NPC), heterochromatin protein 1a (HP1a), H3K9me2-and H3K27me3associated chromatin remained intact. The fluorescence intensity of the DAPI-stained peripheral chromatin significantly decreased and that of the central chromatin significantly increased in the proventriculus nuclei of the mutantflies compared to wild-type. However, the mutation had little effect on chromatin radial distribution inside highly polytenized salivary gland nuclei.

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“…These loci are generally heterochromatic, and genes within LADs are frequently transcriptionally repressed and undergo active silencing, while genes away from the lamina are more often competent for transcriptional activation (Briand and Collas, 2020) . Mutations in nuclear lamins disrupt LAD organization and can cause disease (Briand et al, 2018;Lee et al, 2019;Vadrot et al, 2015;Worman, 2012) .…”

mentioning

confidence: 99%

An atlas of lamina-associated chromatin across twelve human cell types reveals an intermediate chromatin subtype

Keough

Shah

Gjoni

et al. 2020

Preprint

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Three-dimensional genome organization, specifically organization of heterochromatin at the nuclear periphery, coordinates cell type-specific gene regulation. While defining various histone modifications and chromatin-associated proteins in multiple cell types has provided important insights into epigenetic regulation of gene expression and cellular identity, peripheral heterochromatin has not been mapped comprehensively and relatively few examples have emerged detailing the role of peripheral heterochromatin in cellular identity, cell fate choices, and/or organogenesis. In this study, we define nuclear peripheral heterochromatin organization signatures based on association with LAMIN B1 and/or dimethylation of lysine 9 on H3 (H3K9me2) across thirteen human cell types encompassing pluripotent stem cells, intermediate progenitors and differentiated cells from all three germ layers. Genomic analyses across this atlas reveal that lamin-associated chromatin is organized into at least two different compartments, defined by differences in genome coverage, chromatin accessibility, residence of transposable elements, replication timing domains, and gene complements. Our datasets reveal that only a small subset of lamin-associated chromatin domains are cell type invariant, underscoring the complexity of peripheral heterochromatin organization. Moreover, by integrating peripheral chromatin maps with transcriptional data, we find evidence of cooperative shifts between chromatin structure and gene expression associated with each cell type. This atlas of peripheral chromatin provides the largest resource to date for peripheral chromatin organization and a deeper appreciation for how this organization may impact the establishment and maintenance of cellular identity.

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Lamina-associated domains: peripheral matters and internal affairs

Cited by 203 publications

References 159 publications

Live imaging of chromatin distribution in muscle nuclei reveals novel principles of nuclear architecture and chromatin compartmentalization

Live imaging of chromatin distribution in muscle nuclei reveals novel principles of nuclear architecture and chromatin compartmentalization

Reorganization of the nuclear architecture in the Drosophila melanogaster Lamin B mutant lacking the CaaX box

An atlas of lamina-associated chromatin across twelve human cell types reveals an intermediate chromatin subtype

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