scholarly journals Lineage-specific reorganization of nuclear peripheral heterochromatin and H3K9me2 domains

Development ◽  
2019 ◽  
Vol 146 (3) ◽  
pp. dev174078 ◽  
Author(s):  
Kelvin See ◽  
Yemin Lan ◽  
Joshua Rhoades ◽  
Rajan Jain ◽  
Cheryl L. Smith ◽  
...  
Keyword(s):  
Peripheral Heterochromatin

scholarly journals H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Andrey Poleshko ◽  
Cheryl L Smith ◽  
Son C Nguyen ◽  
Priya Sivaramakrishnan ◽  
Karen G Wong ◽  
...  
Keyword(s):  
Cell Division ◽  
Spatial Organization ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Positional Information ◽  
Specific Gene ◽  
Cell Type ◽  
Histone 3 ◽  
Spatial Positioning ◽  
Peripheral Heterochromatin

Cell-type-specific 3D organization of the genome is unrecognizable during mitosis. It remains unclear how essential positional information is transmitted through cell division such that a daughter cell recapitulates the spatial genome organization of the parent. Lamina-associated domains (LADs) are regions of repressive heterochromatin positioned at the nuclear periphery that vary by cell type and contribute to cell-specific gene expression and identity. Here we show that histone 3 lysine 9 dimethylation (H3K9me2) is an evolutionarily conserved, specific mark of nuclear peripheral heterochromatin and that it is retained through mitosis. During mitosis, phosphorylation of histone 3 serine 10 temporarily shields the H3K9me2 mark allowing for dissociation of chromatin from the nuclear lamina. Using high-resolution 3D immuno-oligoFISH, we demonstrate that H3K9me2-enriched genomic regions, which are positioned at the nuclear lamina in interphase cells prior to mitosis, re-associate with the forming nuclear lamina before mitotic exit. The H3K9me2 modification of peripheral heterochromatin ensures that positional information is safeguarded through cell division such that individual LADs are re-established at the nuclear periphery in daughter nuclei. Thus, H3K9me2 acts as a 3D architectural mitotic guidepost. Our data establish a mechanism for epigenetic memory and inheritance of spatial organization of the genome.

scholarly journals LBR and Lamin A/C Sequentially Tether Peripheral Heterochromatin and Inversely Regulate Differentiation

Cell ◽  
2013 ◽  
Vol 152 (3) ◽  
pp. 584-598 ◽  
Author(s):  
Irina Solovei ◽  
Audrey S. Wang ◽  
Katharina Thanisch ◽  
Christine S. Schmidt ◽  
Stefan Krebs ◽  
...  
Keyword(s):  
Lamin A ◽  
Peripheral Heterochromatin

scholarly journals β-Globin cis-elements determine differential nuclear targeting through epigenetic modifications

2013 ◽  
Vol 203 (5) ◽  
pp. 767-783 ◽  
Author(s):  
Qian Bian ◽  
Nimish Khanna ◽  
Jurgis Alvikas ◽  
Andrew S. Belmont
Keyword(s):  
Globin Gene ◽  
Nuclear Periphery ◽  
Artificial Chromosome ◽  
Pericentric Heterochromatin ◽  
Cis Elements ◽  
Nuclear Targeting ◽  
Bac Transgenesis ◽  
Flanking Sequences ◽  
Peripheral Heterochromatin

Increasing evidence points to nuclear compartmentalization as a contributing mechanism for gene regulation, yet mechanisms for compartmentalization remain unclear. In this paper, we use autonomous targeting of bacterial artificial chromosome (BAC) transgenes to reveal cis requirements for peripheral targeting. Three peripheral targeting regions (PTRs) within an HBB BAC bias a competition between pericentric versus peripheral heterochromatin targeting toward the nuclear periphery, which correlates with increased H3K9me3 across the β-globin gene cluster and locus control region. Targeting to both heterochromatin compartments is dependent on Suv39H-mediated H3K9me3 methylation. In different chromosomal contexts, PTRs confer no targeting, targeting to pericentric heterochromatin, or targeting to the periphery. A combination of fluorescent in situ hybridization, BAC transgenesis, and knockdown experiments reveals that peripheral tethering of the endogenous HBB locus depends both on Suv39H-mediated H3K9me3 methylation over hundreds of kilobases surrounding HBB and on G9a-mediated H3K9me2 methylation over flanking sequences in an adjacent lamin-associated domain. Our results demonstrate that multiple cis-elements regulate the overall balance of specific epigenetic marks and peripheral gene targeting.

scholarly journals H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis

2019 ◽  
Author(s):  
Andrey Poleshko ◽  
Cheryl L. Smith ◽  
Son C. Nguyen ◽  
Priya Sivaramakrishnan ◽  
John Isaac Murray ◽  
...  
Keyword(s):  
Cell Division ◽  
Spatial Organization ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Positional Information ◽  
Specific Gene ◽  
Cell Type ◽  
Histone 3 ◽  
Spatial Positioning ◽  
Peripheral Heterochromatin

AbstractCell-type-specific 3D organization of the genome is unrecognizable during mitosis. It remains unclear how essential positional information is transmitted through cell division such that a daughter cell recapitulates the spatial genome organization of the parent. Lamina-associated domains (LADs) are regions of repressive heterochromatin positioned at the nuclear periphery that vary by cell type and contribute to cell-specific gene expression and identity. Here we show that histone 3 lysine 9 dimethylation (H3K9me2) is an evolutionarily conserved, specific mark of nuclear peripheral heterochromatin and that it is retained through mitosis. During mitosis, phosphorylation of histone 3 serine 10 temporarily shields the H3K9me2 mark allowing for dissociation of chromatin from the nuclear lamina. Using high-resolution 3D immuno-oligoFISH, we demonstrate that H3K9me2-enriched genomic regions, which are positioned at the nuclear lamina in interphase cells prior to mitosis, re-associate with the forming nuclear lamina before mitotic exit. The H3K9me2 modification of peripheral heterochromatin ensures that positional information is safeguarded through cell division such that individual LADs are re-established at the nuclear periphery in daughter nuclei. Thus, H3K9me2 acts as a 3D architectural mitotic guidepost. Our data establish a mechanism for epigenetic memory and inheritance of spatial organization of the genome.

Nuclear envelope dynamics

2001 ◽  
Vol 79 (5) ◽  
pp. 533-542 ◽  
Author(s):  
Davide Salina ◽  
Khaldon Bodoor ◽  
Paul Enarson ◽  
Wahyu Hendrati Raharjo ◽  
Brian Burke
Keyword(s):  
Nuclear Envelope ◽  
Mitotic Spindle ◽  
Nuclear Architecture ◽  
Nuclear Pore ◽  
Permeable Barrier ◽  
Macromolecular Trafficking ◽  
Temporal And Spatial ◽  
Peripheral Heterochromatin ◽  
Inner Nuclear Membrane Protein ◽  
Gain Access

The nuclear envelope (NE) provides a semi permeable barrier between the nucleus and cytoplasm and plays a central role in the regulation of macromolecular trafficking between these two compartments. In addition to this transport function, the NE is a key determinant of interphase nuclear architecture. Defects in NE proteins such as A-type lamins and the inner nuclear membrane protein, emerin, result in several human diseases that include cardiac and skeletal myopathies as well as lipodystrophy. Certain disease-linked A-type lamin defects cause profound changes in nuclear organization such as loss of peripheral heterochromatin and redistribution of other nuclear envelope components. While clearly essential in maintenance of nuclear integrity, the NE is a highly dynamic organelle. In interphase it is constantly remodeled to accommodate nuclear growth. During mitosis it must be completely dispersed so that the condensed chromosomes may gain access to the mitotic spindle. Upon completion of mitosis, dispersed NE components are reutilized in the assembly of nuclei within each daughter cell. These complex NE rearrangements are under precise temporal and spatial control and involve interactions with microtubules, chromatin, and a variety of cell-cycle regulatory molecules.Key words: nuclear envelope, lamin, nuclear pore complex, nuclear membranes, mitosis.

scholarly journals Author response: H3K9me2 orchestrates inheritance of spatial positioning of peripheral heterochromatin through mitosis

2019 ◽  
Author(s):  
Andrey Poleshko ◽  
Cheryl L Smith ◽  
Son C Nguyen ◽  
Priya Sivaramakrishnan ◽  
Karen G Wong ◽  
...  
Keyword(s):  
Author Response ◽  
Spatial Positioning ◽  
Peripheral Heterochromatin

scholarly journals KMT1/Suv39 methyltransferase family regulates peripheral heterochromatin tethering via histone and non-histone protein methylations

2018 ◽  
Author(s):  
Radhika Arasala Rao ◽  
Alhad Ashok Ketkar ◽  
Neelam Kedia ◽  
Vignesh K Krishnamoorthy ◽  
Vairavan Lakshmanan ◽  
...  
Keyword(s):  
Aging Process ◽  
Human Fibroblasts ◽  
Nuclear Periphery ◽  
Nuclear Morphology ◽  
Histone Protein ◽  
Histone Methyltransferases ◽  
Domain Organization ◽  
Peripheral Heterochromatin ◽  
Heterochromatin Domain ◽  
Global Reduction

AbstractEuchromatic histone methyltransferases (EHMTs), members of the KMT1 family, methylate histone and non-histone proteins. Here we uncover a novel role for EHMTs in regulating heterochromatin anchorage to the nuclear periphery (NP) via non-histone (LaminB1) methylations. We show that EHMTs methylates and stabilizes LaminB1 (LMNB1), which associates with the H3K9me2-marked peripheral heterochromatin. Loss of LMNB1 methylation or EHMTs abrogates the heterochromatin anchorage from the NP. We further demonstrate that the loss of EHMTs induces many hallmarks of aging including global reduction of H3K27methyl marks along with altered nuclear-morphology. Consistent with this, we observed a gradual depletion of EHMTs, which correlates with loss of methylated LMNB1 and peripheral heterochromatin in aging human fibroblasts. Restoration of EHMT expression reverts peripheral heterochromatin defect in aged cells. Collectively our work elucidates a new mechanism by which EHMTs regulate heterochromatin domain organization and reveals their impact on fundamental changes associated with the intrinsic aging process.

scholarly journals Chromosomal condensation leads to a preference for peripheral heterochromatin

2019 ◽  
Author(s):  
Quinn MacPherson ◽  
Andrew J. Spakowitz
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Nuclear Periphery ◽  
Small Subset ◽  
Histone Tails ◽  
Preferential Binding ◽  
Chromosomal Condensation ◽  
Peripheral Heterochromatin ◽  
Genomic Regions ◽  
Chromatin Density

ABSTRACTA layer of dense heterochromatin is found at the periphery of the nucleus. Because this peripheral heterochromatin functions as a repressive phase, mechanisms that relocate genes to the periphery play an important role in regulating transcription. Using Monte-Carlo simulations, we show that an interaction between chromatin and the nuclear boundary need not be specific to heterochromatin in order to preferentially locate heterochromatin to the nuclear periphery. This observation considerably broadens the class of possible interactions that result in peripheral positioning to include boundary interactions that either weakly attract all chromatin or strongly bind to a randomly chosen small subset of loci. The key distinguishing feature of heterochromatin is its high chromatin density with respect to euchromatin. In our model this densification is caused by HP1’s preferential binding to H3K9me3 marked histone tails. We conclude that factors that are themselves unrelated to the nuclear periphery can determine which genomic regions condense to form heterochromatin and thereby control which regions are relocated to the periphery.

scholarly journals Towards delineating the chain of events that cause premature senescence in the accelerated aging syndrome Hutchinson–Gilford progeria (HGPS)

2020 ◽  
Vol 48 (3) ◽  
pp. 981-991
Author(s):  
Oliver Dreesen
Keyword(s):  
Accelerated Aging ◽  
Nuclear Lamina ◽  
Nucleocytoplasmic Transport ◽  
Cardiovascular Complications ◽  
Premature Aging ◽  
Intermediate Filament Proteins ◽  
Skin Abnormalities ◽  
Transcriptional Changes ◽  
Peripheral Heterochromatin ◽  
Cellular Phenotypes

The metazoan nucleus is equipped with a meshwork of intermediate filament proteins called the A- and B-type lamins. Lamins lie beneath the inner nuclear membrane and serve as a nexus to maintain the architectural integrity of the nucleus, chromatin organization, DNA repair and replication and to regulate nucleocytoplasmic transport. Perturbations or mutations in various components of the nuclear lamina result in a large spectrum of human diseases collectively called laminopathies. One of the most well-characterized laminopathies is Hutchinson–Gilford progeria (HGPS), a rare segmental premature aging syndrome that resembles many features of normal human aging. HGPS patients exhibit alopecia, skin abnormalities, osteoporosis and succumb to cardiovascular complications in their teens. HGPS is caused by a mutation in LMNA, resulting in a mutated form of lamin A, termed progerin. Progerin expression results in a myriad of cellular phenotypes including abnormal nuclear morphology, loss of peripheral heterochromatin, transcriptional changes, DNA replication defects, DNA damage and premature cellular senescence. A key challenge is to elucidate how these different phenotypes are causally and mechanistically linked. In this mini-review, we highlight some key findings and present a model on how progerin-induced phenotypes may be temporally and mechanistically linked.

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