المؤلفون: Kim, Joonyoung R, Kim, Paul H, Presnell, Ashley, Tu, Yiping, Young, Stephen G

المصدر: Nucleus. 14(1)

مصطلحات موضوعية: Biochemistry and Cell Biology, Biological Sciences, Genetics, Animals, Mice, Cell Nucleus, Fibroblasts, Lamin Type A, Mice, Knockout, Lamins, LMNA deficiency, lmna transcripts, nuclear envelope, nuclear lamina, protein farnesylation

الوصف: The Lmna knockout mouse (Lmna-/-) created by Sullivan and coworkers in 1999 has been widely used to examine lamin A/C function. The knockout allele contains a deletion of Lmna intron 7-exon 11 sequences and was reported to be a null allele. Later, Jahn and coworkers discovered that the mutant allele produces a 54-kDa truncated lamin A and identified, by RT-PCR, a Lmna cDNA containing exon 1-7 + exon 12 sequences. Because exon 12 encodes prelamin A's CaaX motif, the mutant lamin A is assumed to be farnesylated. In the current study, we found that the truncated lamin A in Lmna-/- mouse embryonic fibroblasts (MEFs) was predominantly nucleoplasmic rather than at the nuclear rim, leading us to hypothesize that it was not farnesylated. Our study revealed that the most abundant Lmna transcripts in Lmna-/- MEFs contain exon 1-7 but not exon 12 sequences. Exon 1-7 + exon 12 transcripts were detectable by PCR but in trace amounts. We suspect that these findings explain the nucleoplasmic distribution of the truncated lamin A in Lmna-/- MEFs, and subsequent cell transduction experiments support this suspicion. A truncated lamin A containing exon 1-7 sequence was nucleoplasmic, whereas a lamin A containing exon 1-7 + exon 12 sequences was located along the nuclear rim. Our study explains the nucleoplasmic targeting of truncated lamin A in Lmna-/- MEFs and adds to our understanding of a commonly used strain of Lmna-/- mice.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/3m08291nTest

المؤلفون: Shah, Parisha P, Keough, Kathleen C, Gjoni, Ketrin, Santini, Garrett T, Abdill, Richard J, Wickramasinghe, Nadeera M, Dundes, Carolyn E, Karnay, Ashley, Chen, Angela, Salomon, Rachel EA, Walsh, Patrick J, Nguyen, Son C, Whalen, Sean, Joyce, Eric F, Loh, Kyle M, Dubois, Nicole, Pollard, Katherine S, Jain, Rajan

المصدر: Genome Biology. 24(1)

مصطلحات موضوعية: Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Biological Sciences, Stem Cell Research, Genetics, 1.1 Normal biological development and functioning, Underpinning research, Humans, Chromatin, Nuclear Lamina, Cell Nucleus, Chromatin Assembly and Disassembly, Cell Differentiation, Lamina-associated domains, Peripheral chromatin organization, 3D genome, Cellular differentiation, Environmental Sciences, Information and Computing Sciences, Bioinformatics

الوصف: BackgroundAssociation of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via gene silencing. Unlike many histone modifications and chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human cell types, which limits our understanding of the role peripheral chromatin plays in development and disease.ResultsTo address this gap, we map LAMIN B1 occupancy across twelve human cell types encompassing pluripotent stem cells, intermediate progenitors, and differentiated cells from all three germ layers. Integrative analyses of this atlas with gene expression and repressive histone modification maps reveal that lamina-associated chromatin in all twelve cell types is organized into at least two subtypes defined by differences in LAMIN B1 occupancy, gene expression, chromatin accessibility, transposable elements, replication timing, and radial positioning. Imaging of fluorescently labeled DNA in single cells validates these subtypes and shows radial positioning of LADs with higher LAMIN B1 occupancy and heterochromatic histone modifications primarily embedded within the lamina. In contrast, the second subtype of lamina-associated chromatin is relatively gene dense, accessible, dynamic across development, and positioned adjacent to the lamina. Most genes gain or lose LAMIN B1 occupancy consistent with cell types along developmental trajectories; however, we also identify examples where the enhancer, but not the gene body and promoter, changes LAD state.ConclusionsAltogether, this atlas represents the largest resource to date for peripheral chromatin organization studies and reveals an intermediate chromatin subtype.

الوصول الحر: https://escholarship.org/uc/item/3801w97zTest

المؤلفون: Vahabikashi, Amir, Sivagurunathan, Suganya, Nicdao, Fiona Ann Sadsad, Han, Yu Long, Park, Chan Young, Kittisopikul, Mark, Wong, Xianrong, Tran, Joseph R, Gundersen, Gregg G, Reddy, Karen L, Luxton, GW Gant, Guo, Ming, Fredberg, Jeffrey J, Zheng, Yixian, Adam, Stephen A, Goldman, Robert D

المصدر: Proceedings of the National Academy of Sciences of the United States of America. 119(17)

مصطلحات موضوعية: Biochemistry and Cell Biology, Medical Physiology, Biomedical and Clinical Sciences, Biological Sciences, Bioengineering, Aetiology, 2.1 Biological and endogenous factors, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Cell Nucleus, Cytoskeleton, Fibroblasts, Lamin Type A, Lamin Type B, Mice, Nuclear Lamina, Nuclear Matrix, Protein Isoforms, nuclear lamins, LINC complex, cell mechanics, cytoskeleton, mechanobiology

الوصف: The ability of a cell to regulate its mechanical properties is central to its function. Emerging evidence suggests that interactions between the cell nucleus and cytoskeleton influence cell mechanics through poorly understood mechanisms. Here we conduct quantitative confocal imaging to show that the loss of A-type lamins tends to increase nuclear and cellular volume while the loss of B-type lamins behaves in the opposite manner. We use fluorescence recovery after photobleaching, atomic force microscopy, optical tweezer microrheology, and traction force microscopy to demonstrate that A-type lamins engage with both F-actin and vimentin intermediate filaments (VIFs) through the linker of nucleoskeleton and cytoskeleton (LINC) complexes to modulate cortical and cytoplasmic stiffness as well as cellular contractility in mouse embryonic fibroblasts (MEFs). In contrast, we show that B-type lamins predominantly interact with VIFs through LINC complexes to regulate cytoplasmic stiffness and contractility. We then propose a physical model mediated by the lamin–LINC complex that explains these distinct mechanical phenotypes (mechanophenotypes). To verify this model, we use dominant negative constructs and RNA interference to disrupt the LINC complexes that facilitate the interaction of the nucleus with the F-actin and VIF cytoskeletons and show that the loss of these elements results in mechanophenotypes like those observed in MEFs that lack A- or B-type lamin isoforms. Finally, we demonstrate that the loss of each lamin isoform softens the cell nucleus and enhances constricted cell migration but in turn increases migration-induced DNA damage. Together, our findings uncover distinctive roles for each of the four major lamin isoforms in maintaining nucleocytoskeletal interactions and cellular mechanics.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/18x2961tTest

المؤلفون: Sara Escudeiro-Lopes, Vlada V. Filimonenko, Lenka Jarolimová, Pavel Hozák

المصدر: Cells, Vol 13, Iss 5, p 399 (2024)

مصطلحات موضوعية: lamin A/C, phosphorylation, cell nucleus, nuclear lamina, nucleoplasm, phosphoinositides, Cytology, QH573-671

الوصف: Lamins, the nuclear intermediate filaments, are important regulators of nuclear structural integrity as well as nuclear functional processes such as DNA transcription, replication and repair, and epigenetic regulations. A portion of phosphorylated lamin A/C localizes to the nuclear interior in interphase, forming a lamin A/C pool with specific properties and distinct functions. Nucleoplasmic lamin A/C molecular functions are mainly dependent on its binding partners; therefore, revealing new interactions could give us new clues on the lamin A/C mechanism of action. In the present study, we show that lamin A/C interacts with nuclear phosphoinositides (PIPs), and with nuclear myosin I (NM1). Both NM1 and nuclear PIPs have been previously reported as important regulators of gene expression and DNA damage/repair. Furthermore, phosphorylated lamin A/C forms a complex with NM1 in a phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent manner in the nuclear interior. Taken together, our study reveals a previously unidentified interaction between phosphorylated lamin A/C, NM1, and PI(4,5)P2 and suggests new possible ways of nucleoplasmic lamin A/C regulation, function, and importance for the formation of functional nuclear microdomains.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2073-4409/13/5/399Test; https://doaj.org/toc/2073-4409Test

الوصول الحر: https://doaj.org/article/b60eb9da1a83432792bcf938489fbc38Test

المؤلفون: Fang, Yiling, Gu, Yangnan

مصطلحات موضوعية: Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, 1.1 Normal biological development and functioning, Underpinning research, Inflammatory and immune system, Active Transport, Cell Nucleus, Cell Nucleus, Immunity, Innate, Models, Immunological, Nuclear Envelope, Nuclear Pore, Nuclear Pore Complex Proteins, Plant Immunity, Plant Proteins, Plants, Signal Transduction, nuclear envelope, nuclear pore complex, nuclear transport receptors, nucleoskeletal proteins, innate immune system, plant Immunity, nucleocytoplasmic continuum, nuclear lamina, Immunology, Medical Microbiology, Biochemistry and cell biology, Genetics

الوصف: Unlike animals, plants do not have specialized immune cells and lack an adaptive immune system. Instead, plant cells rely on their unique innate immune system to defend against pathogens and coordinate beneficial interactions with commensal and symbiotic microbes. One of the major convergent points for plant immune signaling is the nucleus, where transcriptome reprogramming is initiated to orchestrate defense responses. Mechanisms that regulate selective transport of nuclear signaling cargo and chromatin activity at the nuclear boundary play a pivotal role in immune activation. This review summarizes the current knowledge of how nuclear membrane-associated core protein and protein complexes, including the nuclear pore complex, nuclear transport receptors, and the nucleoskeleton participate in plant innate immune activation and pathogen resistance. We also discuss the role of their functional counterparts in regulating innate immunity in animals and highlight potential common mechanisms that contribute to nuclear membrane-centered immune regulation in higher eukaryotes.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8c1516h3Test

المؤلفون: Karen L. Reddy, Ashley J. Melendez-Perez, Xianrong Wong

المصدر: Cold Spring Harbor perspectives in biology. 14(2)

مصطلحات موضوعية: Cell Nucleus, Nuclear Lamina, Nuclear Envelope, DNA replication, Biology, Mechanotransduction, Cellular, General Biochemistry, Genetics and Molecular Biology, Chromatin, Lamins, Cell biology, medicine.anatomical_structure, RNA splicing, medicine, Inner membrane, Nuclear lamina, Nuclear membrane, Transcription factor, Lamin

الوصف: Lamins interact with a host of nuclear membrane proteins, transcription factors, chromatin regulators, signaling molecules, splicing factors, and even chromatin itself to form a nuclear subcompartment, the nuclear lamina, that is involved in a variety of cellular processes such as the governance of nuclear integrity, nuclear positioning, mitosis, DNA repair, DNA replication, splicing, signaling, mechanotransduction and -sensation, transcriptional regulation, and genome organization. Lamins are the primary scaffold for this nuclear subcompartment, but interactions with lamin-associated peptides in the inner nuclear membrane are self-reinforcing and mutually required. Lamins also interact, directly and indirectly, with peripheral heterochromatin domains called lamina-associated domains (LADs) and help to regulate dynamic 3D genome organization and expression of developmentally regulated genes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c30177ea3f663da5e5dd8644ee0dd143Test
https://pubmed.ncbi.nlm.nih.gov/34400553Test

المؤلفون: Neufeld, Ester, Feinstein, Naomi, Gruenbaum, Yosef, Liu, Jun

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2005 Nov . 102(46), 16690-16695.

الوصول الحر: https://www.jstor.org/stable/4152282Test

المؤلفون: Yongpeng Zeng, Yinyin Zhuang, Benjamin Vinod, Xiangfu Guo, Aninda Mitra, Peng Chen, Isabella Saggio, G. V. Shivashankar, Weibo Gao, Wenting Zhao

المساهمون: School of Biological Sciences, School of Physical and Mathematical Sciences, School of Chemistry, Chemical Engineering and Biotechnology, Institute for Digital Molecular Analytics and Science, NTU, The Photonics Institute, Centre for Disruptive Photonic Technologies (CDPT)

المصدر: Nano Letters. 22:7724-7733

مصطلحات موضوعية: nanopillar, subnuclear irregularity, nuclear lamina, nuclear grading, malignancy, cancer heterogeneity, Cell Nucleus, nanopillar, Nuclear Envelope, Mechanical Engineering, Biological sciences [Science], Cell Count, Cell Differentiation, Bioengineering, General Chemistry, cancer heterogeneity, Condensed Matter Physics, subnuclear irregularity, Neoplasms, Humans, Subnuclear Irregularity, General Materials Science, nuclear lamina, nuclear grading, Nanopillar, malignancy

الوصف: For more than a century, abnormal nuclei in tumor cells, presenting subnuclear invaginations and folds on the nuclear envelope, have been known to be associated with high malignancy and poor prognosis. However, current nuclear morphology analysis focuses on the features of the entire nucleus, overlooking the malignancy-related subnuclear features in nanometer scale. The main technical challenge is to probe such tiny and randomly distributed features inside cells. We here employ nanopillar arrays to guide subnuclear features into ordered patterns, enabling their quantification as a strong indicator of cell malignancy. Both breast and liver cancer cells were validated as well as the quantification of nuclear abnormality heterogeneity. The alterations of subnuclear patterns were also explored as effective readouts for drug treatment. We envision that this nanopillar-enabled quantification of subnuclear abnormal features in tumor cells opens a new angle in characterizing malignant cells and studying the unique nuclear biology in cancer. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) This work is supported by the Singapore Ministry of Education (MOE) (W.Z., RG145/18 and RG112/20), the Singapore National Research Foundation (W.Z., NRF2019-NRF-ISF003- 3292), the Institute for Digital Molecular Analytics and Science (IDMxS) supported by MOE funding under the Research Centres of Excellence scheme (W.Z.), the NTU Start-up Grant (W.Z.), the NTU-NNI Neurotechnology Fellowship (W.Z.), and AIRC IG-24614 and Sapienza AR1181642EE61111 (I.S.).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b1620e5298a58bdc8df4bb1a7bf2f2c4Test
https://doi.org/10.1021/acs.nanolett.2c01849Test

المؤلفون: Schirmer, Eric C., Guan, Tinglu, Gerace, Larry

المصدر: The Journal of Cell Biology, 2001 Apr . 153(3), 479-489.

الوصول الحر: https://www.jstor.org/stable/1620401Test

المؤلفون: Rullens, Pim M J, Kind, Jop

المصدر: Rullens , P M J & Kind , J 2021 , ' Attach and stretch : Emerging roles for genome-lamina contacts in shaping the 3D genome ' , Current Opinion in Cell Biology , vol. 70 , pp. 51-57 . https://doi.org/10.1016/j.ceb.2020.11.006Test

مصطلحات موضوعية: Animals, Cell Nucleus, Chromatin, Genome, Intermediate Filaments, Nuclear Envelope, Nuclear Lamina

الوصف: A large proportion of the metazoan genome is spatially segregated at the nuclear periphery through genomic contacts with the nuclear lamina, a thin meshwork of lamin filaments that lines the inner-nuclear membrane. Lamina-associated domains are believed to contribute to the regulation of gene transcription and to provide structural three-dimensional support to the organization of the genome in A and B compartments and topologically associating domains. In this review, we will evaluate recent work addressing the role of lamina-associated domains in three-dimensional genome organization and propose experimental frameworks that may expand our understanding of their interdependence.

العلاقة: https://pure.knaw.nl/portal/en/publications/8dc15879-f111-4b2f-9adf-872bf4dae48bTest

الإتاحة: https://doi.org/10.1016/j.ceb.2020.11.006Test
https://doi.org/20.500.11755/8dc15879-f111-4b2f-9adf-872bf4dae48bTest
https://pure.knaw.nl/portal/en/publications/8dc15879-f111-4b2f-9adf-872bf4dae48bTest
https://hdl.handle.net/20.500.11755/8dc15879-f111-4b2f-9adf-872bf4dae48bTest