Positioning Heterochromatin at the Nuclear Periphery Suppresses Histone Turnover to Promote Epigenetic Inheritance

Holla, Sahana; Dhakshnamoorthy, Jothy; Folco, H. Diego; Balachandran, Vanivilasini; Xiao, Hua; Sun, Lingling; Wheeler, David; Zofall, Martin; Grewal, Shiv I. S.

doi:10.1016/j.cell.2019.12.004

Cited by 99 publications

(146 citation statements)

References 85 publications

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“…periphery in Amo1 mutants (17), yet we find that silencing is not affected nearly to the same extent by amo1Δ as by boundary deletions, indicating attachment to the nuclear envelope is not how the domain would be constrained. Instead, homologous pairing between the two elements together with TFIIIC binding might define the bottom of the loop (Fig.…”

Section: Discussionmentioning

confidence: 60%

“…Amo1 and its interacting partner RIXC have been proposed to tether the mating-type region to the nuclear periphery in a subnuclear compartment where reduced histone turnover stabilizes heterochromatin (17). The tethering would rely on the association of RIXC with heterochromatin throughout the silent domain and with the B boxes independent of heterochromatin (17). In both RIXC and Amo1 mutants the mating-type region is displaced from the nuclear periphery and silencing defects are observed (17).…”

Section: Discussionmentioning

confidence: 99%

“…First, it was reported that H3K9me is considerably reduced in the mating-type region in mutants lacking the nuclear membrane protein Bqt4 (35). Second, mutants in the nuclear rim protein Amo1 were also reported to reduce H3K9me in the mat2-mat3 region, in particular outside cenH, attributed to defective maintenance (17). In the case of Amo1, reduced H3K9me was accompanied by partial delocalization from the nuclear periphery (17).…”

Section: S6 and S7 Andmentioning

confidence: 99%

“…Second, mutants in the nuclear rim protein Amo1 were also reported to reduce H3K9me in the mat2-mat3 region, in particular outside cenH, attributed to defective maintenance (17). In the case of Amo1, reduced H3K9me was accompanied by partial delocalization from the nuclear periphery (17). In the case of Bqt4, reduced H3K9me was accompanied by partial delocalization from the nuclear periphery specifically during replication (35).…”

Section: S6 and S7 Andmentioning

confidence: 99%

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Integrity of a heterochromatic domain ensured by its boundary elements

Charlton

Jørgensen

Thon

2020

Proc. Natl. Acad. Sci. U.S.A.

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In fission yeast, the inverted repeats IR-L and IR-R function as boundary elements at the edges of a 20-kb silent heterochromatic domain where nucleosomes are methylated at histone H3K9. Each repeat contains a series of B-box motifs physically associated with the architectural TFIIIC complex and with other factors including the replication regulator Sap1 and the Rix1 complex (RIXC). We demonstrate here the activity of these repeats in heterochromatin formation and maintenance. Deletion of the entire IR-R repeat or, to a lesser degree, deletion of just the B boxes impaired the de novo establishment of the heterochromatic domain. Nucleation proceeded normally at the RNA interference (RNAi)-dependent element cenH but subsequent propagation to the rest of the region occurred at reduced rates in the mutants. Once established, heterochromatin was unstable in the mutants. These defects resulted in bistable populations of cells occupying alternate “on” and “off” epigenetic states. Deleting IR-L in combination with IR-R synergistically tipped the balance toward the derepressed state, revealing a concerted action of the two boundaries at a distance. The nuclear rim protein Amo1 has been proposed to tether the mating-type region and its boundaries to the nuclear envelope, where Amo1 mutants displayed milder phenotypes than boundary mutants. Thus, the boundaries might facilitate heterochromatin propagation and maintenance in ways other than just through Amo1, perhaps by constraining a looped domain through pairing.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: S6 and S7 Andmentioning

confidence: 99%

Section: S6 and S7 Andmentioning

confidence: 99%

See 2 more Smart Citations

Integrity of a heterochromatic domain ensured by its boundary elements

Charlton

Jørgensen

Thon

2020

Proc. Natl. Acad. Sci. U.S.A.

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“…The chromatin region containing the mat locus is localized at the nuclear periphery through the cluster formation of boundary elements on the inverted repeat sequence IR-L/R [89]. A recent report demonstrated that the NE localization of mat locus is mediated through an interaction with nucleoporin Amo1 [31] (see Section 6.2).…”

Section: Proteins Attaching Heterochromatic Regions To the Ne In Meiosismentioning

confidence: 99%

Nuclear Envelope Proteins Modulating the Heterochromatin Formation and Functions in Fission Yeast

Hirano

Asakawa

Sakuno

et al. 2020

Cells

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The nuclear envelope (NE) consists of the inner and outer nuclear membranes (INM and ONM), and the nuclear pore complex (NPC), which penetrates the double membrane. ONM continues with the endoplasmic reticulum (ER). INM and NPC can interact with chromatin to regulate the genetic activities of the chromosome. Studies in the fission yeast Schizosaccharomyces pombe have contributed to understanding the molecular mechanisms underlying heterochromatin formation by the RNAi-mediated and histone deacetylase machineries. Recent studies have demonstrated that NE proteins modulate heterochromatin formation and functions through interactions with heterochromatic regions, including the pericentromeric and the sub-telomeric regions. In this review, we first introduce the molecular mechanisms underlying the heterochromatin formation and functions in fission yeast, and then summarize the NE proteins that play a role in anchoring heterochromatic regions and in modulating heterochromatin formation and functions, highlighting roles for a conserved INM protein, Lem2.

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Evolutionary, structural and functional insights in nuclear organisation and nucleocytoplasmic transport in trypanosomes

Padilla‐Mejia,

Field

2023

FEBS Letters

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One of the remarkable features of eukaryotes is the nucleus, delimited by the nuclear envelope (NE), a complex structure and home to the nuclear lamina and nuclear pore complex (NPC). For decades, these structures were believed to be mainly architectural elements and, in the case of the NPC, simply facilitating nucleocytoplasmic trafficking. More recently, the critical roles of the lamina, NPC and other NE constituents in genome organisation, maintaining chromosomal domains and regulating gene expression have been recognised. Importantly, mutations in genes encoding lamina and NPC components lead to pathogenesis in humans, while pathogenic protozoa disrupt the progression of normal development and expression of pathogenesis‐related genes. Here, we review features of the lamina and NPC across eukaryotes and discuss how these elements are structured in trypanosomes, protozoa of high medical and veterinary importance, highlighting lineage‐specific and conserved aspects of nuclear organisation.

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Positioning Heterochromatin at the Nuclear Periphery Suppresses Histone Turnover to Promote Epigenetic Inheritance

Cited by 99 publications

References 85 publications

Integrity of a heterochromatic domain ensured by its boundary elements

Integrity of a heterochromatic domain ensured by its boundary elements

Nuclear Envelope Proteins Modulating the Heterochromatin Formation and Functions in Fission Yeast

Evolutionary, structural and functional insights in nuclear organisation and nucleocytoplasmic transport in trypanosomes

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