Functions of the nuclear envelope and lamina in development and disease

2008 ◽  
Vol 36 (6) ◽  
pp. 1329-1334 ◽  
Author(s):  
Tatiana V. Cohen ◽  
Lidia Hernandez ◽  
Colin L. Stewart
Keyword(s):  
Transcriptional Regulation ◽  
Nuclear Envelope ◽  
Chromatin Organization ◽  
Signalling Pathways ◽  
Mechanical Integrity ◽  
Inherited Diseases ◽  
And Function

Recent findings that some 24 inherited diseases and anomalies are caused by defects in proteins of the NE (nuclear envelope) and lamina have resulted in a fundamental reassessment of the functions of the NE and underlying lamina. Instead of just regarding the NE and lamina as a molecular filtering device, regulating the transfer of macromolecules between the cytoplasm and nucleus, we now envisage the NE/lamina functioning as a key cellular ‘hub’ in integrating critical functions that include chromatin organization, transcriptional regulation, mechanical integrity of the cell and signalling pathways, as well as acting as a key component in the organization and function of the cytoskeleton.

scholarly journals The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Andres Ramirez-Martinez ◽  
Yichi Zhang ◽  
Kenian Chen ◽  
Jiwoong Kim ◽  
Bercin K. Cenik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Envelope ◽  
Envelope Protein ◽  
Transmembrane Protein ◽  
Chromatin Accessibility ◽  
Chromatin Organization ◽  
Potential Contribution ◽  
Molecular Etiology ◽  
And Function

AbstractLamins and transmembrane proteins within the nuclear envelope regulate nuclear structure and chromatin organization. Nuclear envelope transmembrane protein 39 (Net39) is a muscle nuclear envelope protein whose functions in vivo have not been explored. We show that mice lacking Net39 succumb to severe myopathy and juvenile lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression, and metabolism. These abnormalities resemble those of Emery–Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings highlight the role of Net39 at the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and its potential contribution to the molecular etiology of EDMD.

scholarly journals Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope

2015 ◽  
Vol 112 (47) ◽  
pp. E6562-E6570 ◽  
Author(s):  
Shang-Yi A. Tsai ◽  
Jian-Ying Chuang ◽  
Meng-Shan Tsai ◽  
Xiao-fei Wang ◽  
Zheng-Xiong Xi ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Nuclear Envelope ◽  
Chromatin Remodeling ◽  
Behavioral Sensitization ◽  
Specific Protein ◽  
Cellular Regulation ◽  
Sigma 1 Receptor ◽  
Withdrawal Treatment ◽  
Sigma 1

The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER–mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal.

scholarly journals Functions of DEAD box RNA helicases DDX5 and DDX17 in chromatin organization and transcriptional regulation

BMB Reports ◽  
2018 ◽  
Vol 51 (12) ◽  
pp. 613-622 ◽  
Author(s):  
Guillaume Giraud ◽  
Sophie Terrone ◽  
Cyril F. Bourgeois
Keyword(s):  
Transcriptional Regulation ◽  
Chromatin Organization ◽  
Rna Helicases ◽  
Dead Box

scholarly journals Sox transcription factor mediated transcriptional regulation of Robo4 expression and function

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Ganesh Vinayak Samant ◽  
Kallal Pramanik ◽  
Noah Leigh ◽  
Mark Horswill ◽  
Monica Beltrame ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Regulation ◽  
And Function

scholarly journals The histone variant H2A.Z and chromatin remodeler BRAHMA act coordinately and antagonistically to regulate transcription and nucleosome dynamics in Arabidopsis

2018 ◽  
Author(s):  
E. Shannon Torres ◽  
Roger B. Deal
Keyword(s):  
Transcriptional Regulation ◽  
Transcription Factors ◽  
Binding Sites ◽  
Transcriptional Repression ◽  
Nucleosome Positioning ◽  
Chromatin Organization ◽  
Histone H2a ◽  
Nucleosome Dynamics ◽  
Environmentally Responsive ◽  
Context Specific

ABSTRACTPlants adapt to changes in their environment by regulating transcription and chromatin organization. The histone H2A variant H2A.Z and the SWI2/SNF2 ATPase BRAHMA have overlapping roles in positively and negatively regulating environmentally responsive genes in Arabidopsis, but the extent of this overlap was uncharacterized. Both have been associated with various changes in nucleosome positioning and stability in different contexts, but their specific roles in transcriptional regulation and chromatin organization need further characterization. We show that H2A.Z and BRM act both cooperatively and antagonistically to contribute directly to transcriptional repression and activation of genes involved in development and response to environmental stimuli. We identified 8 classes of genes that show distinct relationships between H2A.Z and BRM and their roles in transcription. We found that H2A.Z contributes to a range of different nucleosome properties, while BRM stabilizes nucleosomes where it binds and destabilizes and/or repositions flanking nucleosomes. H2A.Z and BRM contribute to +1 nucleosome destabilization, especially where they coordinately regulate transcription. We also found that at genes regulated by both BRM and H2A.Z, both factors overlap with the binding sites of light-regulated transcription factors PIF4, PIF5, and FRS9, and that some of the FRS9 binding sites are dependent on H2A.Z and BRM for accessibility. Collectively, we comprehensively characterized the antagonistic and cooperative contributions of H2A.Z and BRM to transcriptional regulation, and illuminated their interrelated roles in chromatin organization. The variability observed in their individual functions implies that both BRM and H2A.Z have more context-specific roles within diverse chromatin environments than previously assumed.

scholarly journals Regulation of Energy Expenditure and Brown/Beige Thermogenic Activity by Interleukins: New Roles for Old Actors

2018 ◽  
Vol 19 (9) ◽  
pp. 2569 ◽  
Author(s):  
María García ◽  
Patricia Pazos ◽  
Luis Lima ◽  
Carlos Diéguez
Keyword(s):  
Energy Expenditure ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Molecular Switches ◽  
Metabolic Effects ◽  
Signalling Pathways ◽  
Functional Heterogeneity ◽  
Beige Adipocytes ◽  
The Central Nervous System ◽  
And Function

Obesity rates and the burden of metabolic associated diseases are escalating worldwide Energy burning brown and inducible beige adipocytes in human adipose tissues (ATs) have attracted considerable attention due to their therapeutic potential to counteract the deleterious metabolic effects of nutritional overload and overweight. Recent research has highlighted the relevance of resident and recruited ATs immune cell populations and their signalling mediators, cytokines, as modulators of the thermogenic activity of brown and beige ATs. In this review, we first provide an overview of the developmental, cellular and functional heterogeneity of the AT organ, as well as reported molecular switches of its heat-producing machinery. We also discuss the key contribution of various interleukins signalling pathways to energy and metabolic homeostasis and their roles in the biogenesis and function of brown and beige adipocytes. Besides local actions, attention is also drawn to their influence in the central nervous system (CNS) networks governing energy expenditure.

scholarly journals Piceatannol attenuates RANKL-induced osteoclast differentiation and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promotes Caspase3-mediated apoptosis of mature osteoclasts

2019 ◽  
Vol 6 (6) ◽  
pp. 190360 ◽  
Author(s):  
Liuliu Yan ◽  
Lulu Lu ◽  
Fangbin Hu ◽  
Dattatrya Shetti ◽  
Kun Wei
Keyword(s):  
Bone Resorption ◽  
Osteoclast Differentiation ◽  
Giant Cells ◽  
Inhibitory Effect ◽  
Osteoclast Formation ◽  
Bone Diseases ◽  
Signalling Pathways ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
And Function

Osteoclasts are multinuclear giant cells that have unique ability to degrade bone. The search for new medicines that modulate the formation and function of osteoclasts is a potential approach for treating osteoclast-related bone diseases. Piceatannol (PIC) is a natural organic polyphenolic stilbene compound found in diverse plants with a strong antioxidant and anti-inflammatory effect. However, the effect of PIC on bone health has not been scrutinized systematically. In this study, we used RAW264.7, an osteoclast lineage of cells of murine macrophages, to investigate the effects and the underlying mechanisms of PIC on osteoclasts. Here, we demonstrated that PIC treatment ranging from 0 to 40 µM strongly inhibited osteoclast formation and bone resorption in a dose-dependent manner. Furthermore, the inhibitory effect of PIC was accompanied by the decrease of osteoclast-specific genes. At the molecular level, PIC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), NF-κB p65, IκBα and AKT. Besides, PIC promoted the apoptosis of mature osteoclasts by inducing caspase-3 expression. In conclusion, our results suggested that PIC inhibited RANKL-induced osteoclastogenesis and bone resorption by suppressing MAPK, NF-κB and AKT signalling pathways and promoted caspase3-mediated apoptosis of mature osteoclasts, which might contribute to the treatment of bone diseases characterized by excessive bone resorption.

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