Competition, Fragmentation and Polarization: A Bifurcated International Legal Infrastructure Regarding the Nuclear Architecture and Regulation?

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.

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Lamin A/C Is Dispensable to Mechanical Repression of Adipogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22126580 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6580

Author(s):

Matthew Goelzer ◽

Amel Dudakovic ◽

Melis Olcum ◽

Buer Sen ◽

Engin Ozcivici ◽

...

Keyword(s):

Cell Structure ◽

Nuclear Architecture ◽

Focal Adhesions ◽

Protein Translation ◽

Lamin A ◽

Transcriptional Level ◽

Rna Seq ◽

Interferon Signaling ◽

Regulate Protein ◽

Low Intensity Vibration

Mesenchymal stem cells (MSCs) maintain the musculoskeletal system by differentiating into multiple lineages, including osteoblasts and adipocytes. Mechanical signals, including strain and low-intensity vibration (LIV), are important regulators of MSC differentiation via control exerted through the cell structure. Lamin A/C is a protein vital to the nuclear architecture that supports chromatin organization and differentiation and contributes to the mechanical integrity of the nucleus. We investigated whether lamin A/C and mechanoresponsiveness are functionally coupled during adipogenesis in MSCs. siRNA depletion of lamin A/C increased the nuclear area, height, and volume and decreased the circularity and stiffness. Lamin A/C depletion significantly decreased markers of adipogenesis (adiponectin, cellular lipid content) as did LIV treatment despite depletion of lamin A/C. Phosphorylation of focal adhesions in response to mechanical challenge was also preserved during loss of lamin A/C. RNA-seq showed no major adipogenic transcriptome changes resulting from LIV treatment, suggesting that LIV regulation of adipogenesis may not occur at the transcriptional level. We observed that during both lamin A/C depletion and LIV, interferon signaling was downregulated, suggesting potentially shared regulatory mechanism elements that could regulate protein translation. We conclude that the mechanoregulation of adipogenesis and the mechanical activation of focal adhesions function independently from those of lamin A/C.

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LINCking the Nuclear Envelope to Sperm Architecture

Genes ◽

10.3390/genes12050658 ◽

2021 ◽

Vol 12 (5) ◽

pp. 658

Author(s):

Francesco Manfrevola ◽

Florian Guillou ◽

Silvia Fasano ◽

Riccardo Pierantoni ◽

Rosanna Chianese

Keyword(s):

Nuclear Envelope ◽

Male Fertility ◽

Nuclear Architecture ◽

Sperm Cells ◽

Bridge Structure ◽

Linc Complex ◽

Head Formation ◽

Morphological Maturation ◽

Integral Proteins ◽

Sun Domain

Nuclear architecture undergoes an extensive remodeling during spermatogenesis, especially at levels of spermatocytes (SPC) and spermatids (SPT). Interestingly, typical events of spermiogenesis, such as nuclear elongation, acrosome biogenesis, and flagellum formation, need a functional cooperation between proteins of the nuclear envelope and acroplaxome/manchette structures. In addition, nuclear envelope plays a key role in chromosome distribution. In this scenario, special attention has been focused on the LINC (linker of nucleoskeleton and cytoskeleton) complex, a nuclear envelope-bridge structure involved in the connection of the nucleoskeleton to the cytoskeleton, governing mechanotransduction. It includes two integral proteins: KASH- and SUN-domain proteins, on the outer (ONM) and inner (INM) nuclear membrane, respectively. The LINC complex is involved in several functions fundamental to the correct development of sperm cells such as head formation and head to tail connection, and, therefore, it seems to be important in determining male fertility. This review provides a global overview of the main LINC complex components, with a special attention to their subcellular localization in sperm cells, their roles in the regulation of sperm morphological maturation, and, lastly, LINC complex alterations associated to male infertility.

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The Meiosis-Specific Crs1 Cyclin Is Required for Efficient S-Phase Progression and Stable Nuclear Architecture

International Journal of Molecular Sciences ◽

10.3390/ijms22115483 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5483

Author(s):

Luisa F. Bustamante-Jaramillo ◽

Celia Ramos ◽

Cristina Martín-Castellanos

Keyword(s):

Cell Cycle ◽

Translational Control ◽

Cell Cycle Progression ◽

Nuclear Architecture ◽

Strand Break ◽

Spindle Pole ◽

S Phase ◽

Cycle Progression ◽

Single Wave ◽

Phase Progression

Cyclins and CDKs (Cyclin Dependent Kinases) are key players in the biology of eukaryotic cells, representing hubs for the orchestration of physiological conditions with cell cycle progression. Furthermore, as in the case of meiosis, cyclins and CDKs have acquired novel functions unrelated to this primal role in driving the division cycle. Meiosis is a specialized developmental program that ensures proper propagation of the genetic information to the next generation by the production of gametes with accurate chromosome content, and meiosis-specific cyclins are widespread in evolution. We have explored the diversification of CDK functions studying the meiosis-specific Crs1 cyclin in fission yeast. In addition to the reported role in DSB (Double Strand Break) formation, this cyclin is required for meiotic S-phase progression, a canonical role, and to maintain the architecture of the meiotic chromosomes. Crs1 localizes at the SPB (Spindle Pole Body) and is required to stabilize the cluster of telomeres at this location (bouquet configuration), as well as for normal SPB motion. In addition, Crs1 exhibits CDK(Cdc2)-dependent kinase activity in a biphasic manner during meiosis, in contrast to a single wave of protein expression, suggesting a post-translational control of its activity. Thus, Crs1 displays multiple functions, acting both in cell cycle progression and in several key meiosis-specific events.

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