Networking in the nucleus: a spotlight on LEM-domain proteins

Barton, Lacy J.; Soshnev, Alexey A.; Geyer, Pamela

doi:10.1016/j.ceb.2015.03.005

Cited by 170 publications

(153 citation statements)

References 73 publications

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“…Furthermore, we show that Lem2 interacts with centromeric chromatin via its N terminus that contains the LEM domain. Since LEM proteins have been broadly thought to be involved in heterochromatin tethering (Brachner and Foisner 2011;Barton et al 2015), a plausible model would be that silencing by Lem2 is mediated through tethering these chromatin domains to the nuclear periphery via its LEM domain. However, we provide several lines of experimental evidence that argue against such a simple mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…The LEM domain binds to the metazoan-specific barrier to autointegration factors (BAFs), which are sequence-independent DNA-binding proteins. It has been proposed that their interaction with LEM domain proteins might contribute to gene repression (Margalit et al 2007;Barton et al 2015), but whether BAF proteins bind specifically to heterochromatin is unknown. LAPs have also been reported to interact directly with histone deacetylases (HDACs) and mediate their recruitment to the nuclear periphery (Somech et al 2005;Demmerle et al 2012).…”

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confidence: 99%

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Control of heterochromatin localization and silencing by the nuclear membrane protein Lem2

et al. 2016

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Transcriptionally silent chromatin localizes to the nuclear periphery, which provides a special microenvironment for gene repression. A variety of nuclear membrane proteins interact with repressed chromatin, yet the functional role of these interactions remains poorly understood. Here, we show that, in Schizosaccharomyces pombe, the nuclear membrane protein Lem2 associates with chromatin and mediates silencing and heterochromatin localization. Unexpectedly, we found that these functions can be separated and assigned to different structural domains within Lem2, excluding a simple tethering mechanism. Chromatin association and tethering of centromeres to the periphery are mediated by the N-terminal LEM (LAP2-Emerin-MAN1) domain of Lem2, whereas telomere anchoring and heterochromatin silencing require exclusively its conserved C-terminal MSC (MAN1-Src1 C-terminal) domain. Particularly, silencing by Lem2 is epistatic with the Snf2/HDAC (histone deacetylase) repressor complex SHREC at telomeres, while its necessity can be bypassed by deleting Epe1, a JmjC protein with anti-silencing activity. Furthermore, we found that loss of Lem2 reduces heterochromatin association of SHREC, which is accompanied by increased binding of Epe1. This reveals a critical function of Lem2 in coordinating these antagonistic factors at heterochromatin. The distinct silencing and localization functions mediated by Lem2 suggest that these conserved LEM-containing proteins go beyond simple tethering to play active roles in perinuclear silencing.

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Section: Discussionmentioning

confidence: 99%

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Control of heterochromatin localization and silencing by the nuclear membrane protein Lem2

et al. 2016

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“…The inner and outer nuclear membranes connect via nuclear pores that mediate communication between the cytoplasmic and nucleoplasmic compartments. The inner nuclear membrane is mechanically supported by the nuclear lamina which consists of filamentous lamin proteins (lamins A, B, and C), and several integral membrane proteins, including LEM-domain containing members, LAP2, emerin, and MAN1 [21]. The nuclear lamina is a dynamic structure that associates with chromatin domains and regulates the global organization of chromatin and gene expression [22,23].…”

Section: The Nucleus: Linking Structural Form To Functionmentioning

confidence: 99%

Mechanotransduction and nuclear function

Graham

Burridge

2016

Current Opinion in Cell Biology

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Many signaling pathways converge on the nucleus to regulate critical nuclear events such as transcription, DNA replication and cell cycle progression. While the vast majority of research in this area has focused on signals generated in response to hormones or other soluble factors, the nucleus also responds to mechanical forces. During the past decade or so, much has been learned about how mechanical force can affect transcription, as well as the growth and differentiation of cells. Much has also been learned about how force is transmitted via the cytoskeleton to the nucleus and then across the nuclear envelope to the nuclear lamina and chromatin. In this brief review, we focus on some of the key proteins that transmit mechanical signals across the nuclear envelope.

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“…LEM-2 is also referred to in the literature as Ce-MAN1. Like their mammalian counterparts, emerin and LEMD2, respectively, EMR-1 and LEM-2 have transmembrane domains and are integral INM proteins (Lee et al 2000; for a general review on LEM-domain proteins see Barton et al 2015). EMR-1 and LEM-2 are expressed in all C. elegans cells and are thought to have overlapping functions, as downregulation of both genes by RNA interference (RNAi), but not each gene alone, results in embryonic lethality (Liu et al 2003).…”

Section: Components Of the Nementioning

confidence: 99%

Cell Biology of theCaenorhabditis elegansNucleus

Cohen-Fix

Askjaer

2017

Genetics

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Studies on the Caenorhabditis elegans nucleus have provided fascinating insight to the organization and activities of eukaryotic cells. Being the organelle that holds the genetic blueprint of the cell, the nucleus is critical for basically every aspect of cell biology. The stereotypical development of C. elegans from a one cell-stage embryo to a fertile hermaphrodite with 959 somatic nuclei has allowed the identification of mutants with specific alterations in gene expression programs, nuclear morphology, or nuclear positioning. Moreover, the early C. elegans embryo is an excellent model to dissect the mitotic processes of nuclear disassembly and reformation with high spatiotemporal resolution. We review here several features of the C. elegans nucleus, including its composition, structure, and dynamics. We also discuss the spatial organization of chromatin and regulation of gene expression and how this depends on tight control of nucleocytoplasmic transport. Finally, the extensive connections of the nucleus with the cytoskeleton and their implications during development are described. Most processes of the C. elegans nucleus are evolutionarily conserved, highlighting the relevance of this powerful and versatile model organism to human biology.KEYWORDS Caenorhabditis elegans; chromatin; gene expression; lamin; LEM-domain proteins; LINC; P granule; nuclear pore complex; nuclear envelope; nucleocytoplasmic transport; nucleolus; WormBook TABLE OF CONTENTSAbstract 25 C. elegans as a model system to study cell biology of the nucleus 26 Structural components of the nucleus 27

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Networking in the nucleus: a spotlight on LEM-domain proteins

Cited by 170 publications

References 73 publications

Control of heterochromatin localization and silencing by the nuclear membrane protein Lem2

Control of heterochromatin localization and silencing by the nuclear membrane protein Lem2

Mechanotransduction and nuclear function

Cell Biology of theCaenorhabditis elegansNucleus

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