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Stewart, C. & Burke, B. Teratocarcinoma stem cells and early mouse embryos contain only a single major lamin polypeptide closely resembling lamin B. Cell 51, 383-392

Harvard University, Cambridge, Massachusetts, United States
Cell (Impact Factor: 32.24). 12/1987; 51(3):383-92. DOI: 10.1016/0092-8674(87)90634-9
Source: PubMed

ABSTRACT

The nuclear lamina in adult mammalian somatic cells is composed of three major proteins, lamins A, B, and C. The expression of these proteins during the differentiation of teratocarcinomas and mouse embryogenesis is described. Embryos up to day 8 of gestation and embryonal carcinoma (EC) cells express only a single lamin species closely resembling, if not identical to, lamin B. Lamins A and/or C were detected in fertilized eggs, but disappear during the first 2-4 cleavage divisions, only reappearing in 8 day post-implantation embryos. These two lamins are absent from EC cells, but are strongly expressed in some of their derivatives. These results show that cells of the early mouse embryo do not have a functional requirement for lamins A and C and imply that the structural organization of the nucleus may change fundamentally during embryogenesis.

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    • "In vertebrates, lamin proteins have been divided into A and B types, based on sequence homologies. Whereas B-type lamins are ubiquitously expressed, A-type lamins, such as lamin A and C (hereafter lamin A/C), are developmentally regulated, being absent in the early embryo and expressed in differentiating cells (Stewart and Burke, 1987; Röber et al., 1989), suggesting a role in cell differentiation (Lanzuolo, 2012; Collas et al., 2014). Indeed, beyond providing mechanical support to the nucleus, lamins are involved in the regulation of gene expression at various levels (Shumaker et al., 2006; Scaffidi and Misteli, 2008; Méjat et al., 2009; Lund et al., 2013; McCord et al., 2013). "
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    ABSTRACT: Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors and how this cross talk influences physiological processes is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that tannin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors.
    No preview · Article · Nov 2015 · The Journal of Cell Biology
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    • "Supplemental Material can be found at: 2006; Eckersley-Maslin et al., 2013). LB1 continues to be expressed in all cell types throughout development while LA/C and LB2 expression varies across tissues (Stewart and Burke, 1987; Rober et al., 1989). A large number of mutations in the LMNA gene causing a wide range of genetic disorders, collectively called laminopathies, often cause misshapen nuclei accompanied by significant changes in chromatin organization (Shimi et al., 2008). "
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    ABSTRACT: The nuclear lamina is a key structural element of the metazoan nucleus. However, the structural organization of the major proteins composing the lamina remains poorly defined. Using three-dimensional Structured Illumination Microscopy and computational image analysis, we have characterized the supramolecular structures of lamin A, C, B1 and B2 in mouse embryo fibroblast nuclei. Each isoform forms a distinct fiber meshwork, having comparable physical characteristics with respect to mesh edge length, mesh face area and shape, and edge connectivity to form faces. Some differences were found in face areas between isoforms due to variation in the edge lengths and number of edges per face, suggesting that each meshwork has somewhat unique assembly characteristics. In fibroblasts null for the expression of either lamins A/C or lamin B1, the remaining lamin meshworks are altered compared with the lamin meshworks in wild type nuclei or nuclei lacking lamin B2. Nuclei lacking LA/C exhibit slightly enlarged meshwork faces and some shape changes, whereas LB1-deficient nuclei exhibit primarily a substantial increase in face area. These studies demonstrate that individual lamin isoforms assemble into complex networks within the nuclear lamina and that A-type and B-type lamins have distinct roles in maintaining the organization of the nuclear lamina.
    Full-text · Article · Aug 2015 · Molecular biology of the cell
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    • "Immunofluorescence staining and immunoblotting with isotype specific anti-Lamin antibodies in mouse embryos show low expression of Lamin A/C in ESCs, which increases as cells differentiate (Constantinescu et al., 2006; Eckersley-Maslin et al., 2013). In mice, the increase in Lamin A/C expression is initiated as early as embryonic day 9 and as late as in the adult animal depending on the tissue type (Stewart and Burke, 1987; Rober et al., 1989). In direct support of a role for Lamin A in cell differentiation, experiments in mouse cells testing the effect of Lamin A levels on somatic to iPS cell reprogramming show that depletion of Lamin A accelerates the transition to pluripotency, while cells overexpressing Lamin A take longer to reprogram (Zuo et al., 2012). "
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    ABSTRACT: The eukaryotic cell nucleus houses an organism's genome and is the location within the cell where all signaling induced and development-driven gene expression programs are ultimately specified. The genome is enclosed and separated from the cytoplasm by the nuclear envelope (NE), a double-lipid membrane bilayer, which contains a large variety of trans-membrane and associated protein complexes. In recent years, research regarding multiple aspects of the cell nucleus points to a highly dynamic and coordinated concert of efforts between chromatin and the NE in regulation of gene expression. Details of how this concert is orchestrated and how it directs cell differentiation and disease are coming to light at a rapid pace. Here we review existing and emerging concepts of how interactions between the genome and the NE may contribute to tissue specific gene expression programs to determine cell fate.
    Full-text · Article · Mar 2015 · Frontiers in Genetics
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