scholarly journals Colocalization of intranuclear lamin foci with RNA splicing factors

1999 ◽  
Vol 112 (24) ◽  
pp. 4651-4661 ◽  
Author(s):  
G. Jagatheesan ◽  
S. Thanumalayan ◽  
B. Muralikrishna ◽  
N. Rangaraj ◽  
A.A. Karande ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Rna Splicing ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Splicing Factors ◽  
Lamin A ◽  
Lamin B1 ◽  
Differential Reactivity ◽  
Fibrous Network

The lamins form a fibrous network underlying the inner nuclear membrane termed the nuclear lamina. In order to gain insights into the role of lamins in nuclear organization, we have characterized a monoclonal antibody (LA-2H10) raised against recombinant rat lamin A that labels nuclei in a speckled pattern in all cells of unsynchronized populations of HeLa and rat F-111 fibroblast cells, unlike the typical nuclear periphery staining by another monoclonal antibody to lamin A, LA-2B3. In immunolocalization studies the lamin A speckles or foci were found to colocalize with the RNA splicing factors SC-35 and U5-116 kD, but not with p80 coilin found in coiled bodies. Lamin B1 was also associated with these foci. These foci dispersed when cells entered mitosis and reformed during anaphase. The differential reactivity of LA-2H10 and LA-2B3 was retained after nuclei were extracted with detergents, nucleases and salt to disrupt interactions of lamins with chromatin and other nuclear proteins. Using deletion fragments of recombinant lamin A, the epitope recognized by LA-2H10 was located between amino acids 171 and 246. Our findings are consistent with a structural role for lamins in supporting nuclear compartments containing proteins involved in RNA splicing.

scholarly journals Deformation of the nucleus by TGFβ1 via the remodeling of nuclear envelope and histone isoforms

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Ya-Hui Chi ◽  
Wan-Ping Wang ◽  
Ming-Chun Hung ◽  
Gunn-Guang Liou ◽  
Jing-Ya Wang ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Cell Lines ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Lamin A ◽  
Nuclear Deformation ◽  
Smad Signaling ◽  
Lamin B1 ◽  
Compositional Changes ◽  
Nucleosomal Structure

AbstractThe cause of nuclear shape abnormalities which are often seen in pre-neoplastic and malignant tissues is not clear. In this study we report that deformation of the nucleus can be induced by TGFβ1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFβ1-induced nuclear deformation, a process of which requires incorporation of the nuclear envelope (NE) proteins lamin B1 and SUN1. During this process, the NE constitutively ruptured and reformed. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, clustering at the nuclear periphery and reintegrating into the nucleoplasm. The chromatin regions that lost NE coverage formed a supra-nucleosomal structure characterized by elevated histone H3K27me3 and histone H1, the formation of which depended on the presence of lamin A. These results provide evidence that shape of the nucleus can be modulated through TGFβ1-induced compositional changes in the chromatin and nuclear lamina.

scholarly journals Deformation of the nucleus by TGFβ1 via the remodeling of nuclear envelope and histone isoforms

2021 ◽  
Author(s):  
Ya-Hui Chi ◽  
Wan-Ping Wang ◽  
Ming-Chun Hung ◽  
Gunn-Guang Liou ◽  
Jing-Ya Wang ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Dna Damage Response ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Lamin A ◽  
Nuclear Deformation ◽  
Lamin B1 ◽  
Damage Response ◽  
Compositional Changes ◽  
Nucleosomal Structure

Abstract The cause of nuclear shape abnormalities which are often seen in pre-neoplastic and malignant tissues is not clear. In this study we report that deformation of the nucleus can be induced by TGFβ1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFβ1-induced nuclear deformation, a process of which requires incorporation of the nuclear envelope (NE) proteins lamin B1 and SUN1. During this process, the NE constitutively ruptured and reformed with no observable indications of DNA damage response. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, shuttling between the nucleus and cytoplasm, and clustering at the nuclear periphery. The chromatin regions that lost NE coverage formed a supra-nucleosomal structure characterized by elevated histone H3K27me3 and histone H1, the formation of which depended on the presence of lamin A. These results provide evidence that shape of the nucleus can be modulated through TGFβ1-induced compositional changes in the chromatin and nuclear lamina.

scholarly journals Deformation of the nucleus by TGFβ1 via the remodeling of nuclear envelope and histone isoforms

2021 ◽  
Author(s):  
Ya-Hui Chi ◽  
Wan-Ping Wang ◽  
Ming-Chun Hung ◽  
Gunn-Guang Liou ◽  
Jing-Ya Wang ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Dna Damage Response ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Lamin A ◽  
Nuclear Deformation ◽  
Lamin B1 ◽  
Damage Response ◽  
Compositional Changes ◽  
Nucleosomal Structure

Abstract The cause of nuclear shape abnormalities which are often seen in pre-neoplastic and malignant tissues is not clear. In this study we report that deformation of the nucleus can be induced by TGFb1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFb1-induced nuclear deformation, a process of which requires incorporation of the nuclear envelope (NE) proteins lamin B1 and SUN1. During this process, the NE constitutively ruptured and reformed with no observable indications of DNA damage response. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, shuttling between the nucleus and cytoplasm, and clustering at the nuclear periphery. The chromatin regions that lost NE coverage formed a supra-nucleosomal structure characterized by elevated histone H3K27me3 and histone H1, the formation of which depended on the presence of lamin A. These results provide evidence that shape of the nucleus can be modulated through TGFb1-induced compositional changes in the chromatin and nuclear lamina.

scholarly journals Deformation of the Nucleus by TGFβ1 Via the Remodeling of Nuclear Envelope and Histone Isoforms

2021 ◽  
Author(s):  
Ya-Hui Chi ◽  
Wan-Ping Wang ◽  
Ming-Chun Hung ◽  
Gunn-Guang Liou ◽  
Jing-Ya Wang ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Dna Damage Response ◽  
Nuclear Periphery ◽  
Nuclear Lamina ◽  
Lamin A ◽  
Nuclear Deformation ◽  
Lamin B1 ◽  
Damage Response ◽  
Compositional Changes ◽  
Nucleosomal Structure

Abstract The cause of nuclear shape abnormalities which are often seen in pre-neoplastic and malignant tissues is not clear. In this study we report that deformation of the nucleus can be induced by TGFb1 stimulation in several cell lines including Huh7. In our results, the upregulated histone H3.3 expression downstream of SMAD signaling contributed to TGFb1-induced nuclear deformation, a process of which requires incorporation of the nuclear envelope (NE) proteins lamin B1 and SUN1. During this process, the NE constitutively ruptured and reformed with no observable indications of DNA damage response. Contrast to lamin B1 which was relatively stationary around the nucleus, the upregulated lamin A was highly mobile, shuttling between the nucleus and cytoplasm, and clustering at the nuclear periphery. The chromatin regions that lost NE coverage formed a supra-nucleosomal structure characterized by elevated histone H3K27me3 and histone H1, the formation of which depended on the presence of lamin A. These results provide evidence that shape of the nucleus can be modulated through TGFb1-induced compositional changes in the chromatin and nuclear lamina.

scholarly journals Lamin A/C speckles mediate spatial organization of splicing factor compartments and RNA polymerase II transcription

2002 ◽  
Vol 159 (5) ◽  
pp. 783-793 ◽  
Author(s):  
R. Ileng Kumaran ◽  
Bhattiprolu Muralikrishna ◽  
Veena K. Parnaik
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Hela Cells ◽  
Rna Splicing ◽  
Spatial Organization ◽  
Nuclear Periphery ◽  
Splicing Factor ◽  
Splicing Factors ◽  
Lamin A ◽  
Pol Ii

The A-type lamins have been observed to colocalize with RNA splicing factors in speckles within the nucleus, in addition to their typical distribution at the nuclear periphery. To understand the functions of lamin speckles, the effects of transcriptional inhibitors known to modify RNA splicing factor compartments (SFCs) were examined. Treatment of HeLa cells with α-amanitin or 5,6-dichlorobenzimidazole riboside (DRB) inhibited RNA polymerase II (pol II) transcription and led to the enlargement of lamin speckles as well as SFCs. Removal of the reversible inhibitor DRB resulted in the reactivation of transcription and a rapid, synchronous redistribution of lamins and splicing factors to normal-sized speckles, indicating a close association between lamin speckles and SFCs. Conversely, the expression of NH2-terminally modified lamin A or C in HeLa cells brought about a loss of lamin speckles, depletion of SFCs, and down-regulation of pol II transcription without affecting the peripheral lamina. Our results suggest a unique role for lamin speckles in the spatial organization of RNA splicing factors and pol II transcription in the nucleus.

scholarly journals Lamin B1 acetylation slows the G1 to S cell cycle transition through inhibition of DNA repair

2021 ◽  
Author(s):  
Laura A Murray-Nerger ◽  
Joshua L Justice ◽  
Pranav Rekapalli ◽  
Josiah E Hutton ◽  
Ileana M Cristea
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Posttranslational Modifications ◽  
Cell Cycle Progression ◽  
Nuclear Periphery ◽  
Virus Production ◽  
Nuclear Lamina ◽  
Regulatory Function ◽  
Herpesvirus Type ◽  
Lamin B1

Abstract The integrity and regulation of the nuclear lamina is essential for nuclear organization and chromatin stability, with its dysregulation being linked to laminopathy diseases and cancer. Although numerous posttranslational modifications have been identified on lamins, few have been ascribed a regulatory function. Here, we establish that lamin B1 (LMNB1) acetylation at K134 is a molecular toggle that controls nuclear periphery stability, cell cycle progression, and DNA repair. LMNB1 acetylation prevents lamina disruption during herpesvirus type 1 (HSV-1) infection, thereby inhibiting virus production. We also demonstrate the broad impact of this site on laminar processes in uninfected cells. LMNB1 acetylation negatively regulates canonical nonhomologous end joining by impairing the recruitment of 53BP1 to damaged DNA. This defect causes a delay in DNA damage resolution and a persistent activation of the G1/S checkpoint. Altogether, we reveal LMNB1 acetylation as a mechanism for controlling DNA repair pathway choice and stabilizing the nuclear periphery.

scholarly journals Concentration-dependent lamin assembly and its roles in the localization of other nuclear proteins

2014 ◽  
Vol 25 (8) ◽  
pp. 1287-1297 ◽  
Author(s):  
Yuxuan Guo ◽  
Youngjo Kim ◽  
Takeshi Shimi ◽  
Robert D. Goldman ◽  
Yixian Zheng
Keyword(s):  
Nuclear Lamina ◽  
Nuclear Pore ◽  
Lamin A ◽  
Nuclear Pore Complexes ◽  
Developmental Defects ◽  
Protein Levels ◽  
Lamin B1 ◽  
Mouse Cells ◽  
Pore Complexes ◽  
And Function

The nuclear lamina (NL) consists of lamin polymers and proteins that bind to the polymers. Disruption of NL proteins such as lamin and emerin leads to developmental defects and human diseases. However, the expression of multiple lamins, including lamin-A/C, lamin-B1, and lamin-B2, in mammals has made it difficult to study the assembly and function of the NL. Consequently, it has been unclear whether different lamins depend on one another for proper NL assembly and which NL functions are shared by all lamins or are specific to one lamin. Using mouse cells deleted of all or different combinations of lamins, we demonstrate that the assembly of each lamin into the NL depends primarily on the lamin concentration present in the nucleus. When expressed at sufficiently high levels, each lamin alone can assemble into an evenly organized NL, which is in turn sufficient to ensure the even distribution of the nuclear pore complexes. By contrast, only lamin-A can ensure the localization of emerin within the NL. Thus, when investigating the role of the NL in development and disease, it is critical to determine the protein levels of relevant lamins and the intricate shared or specific lamin functions in the tissue of interest.

scholarly journals Role of the Constitutive Splicing Factors U2AF65and SAP49 in Suboptimal RNA Splicing of Novel Retroviral Mutants

1998 ◽  
Vol 273 (24) ◽  
pp. 15169-15176 ◽  
Author(s):  
John Bouck ◽  
Xiang-Dong Fu ◽  
Anna Marie Skalka ◽  
Richard A. Katz
Keyword(s):  
Rna Splicing ◽  
Splicing Factors ◽  
Constitutive Splicing

scholarly journals Genome-wide maps of nucleolus interactions reveal distinct layers of repressive chromatin domains

2020 ◽  
Author(s):  
Cristiana Bersaglieri ◽  
Jelena Kresoja-Rakic ◽  
Shivani Gupta ◽  
Dominik Bär ◽  
Rostyslav Kuzyakiv ◽  
...  
Keyword(s):  
Nuclear Periphery ◽  
Interaction Strength ◽  
Nuclear Lamina ◽  
Nuclear Space ◽  
Chromosome Architecture ◽  
Neural Genes ◽  
Repressive Chromatin ◽  
Genome Wide ◽  
Nuclear Environment

AbstractEukaryotic chromosomes are folded into hierarchical domains, enabling the organization of the genome into functional compartments. Nuclear periphery and nucleolus are two nuclear landmarks thought to contribute to repressive chromosome architecture. However, while the role of nuclear lamina (NL) in genome organization has been well documented, the function of the nucleolus remains under-investigated due to the lack of methods for genome-wide maps of nucleolar associated domains (NADs). Here we established a method based on a Dam-fused engineered nucleolar histone H2B that marks DNA contacting the nucleolus. NAD-maps of ESCs and neural progenitors revealed layers of genome compartmentalization with distinct, repressive chromatin states based on the interaction with the nucleolus, NL, or both. NADs showed higher H3K9me2 and lower H3K27me3 content than regions exclusively interacting with NL. Upon ESC differentiation, chromosomes around the nucleolus acquire a more compact, rigid architecture whereas NADs specific for ESCs decrease their interaction strength within the repressive B-compartment strength, unlocking neural genes from repressive nuclear environment. The methodologies here developed will make possible to include the contribution of the nucleolus in future studies investigating the relationship between nuclear space and genome function.

Expression of nuclear lamins during mouse preimplantation development

Development ◽  
1988 ◽  
Vol 102 (2) ◽  
pp. 271-278
Author(s):  
E. Houliston ◽  
M.N. Guilly ◽  
J.C. Courvalin ◽  
B. Maro
Keyword(s):  
Cell Differentiation ◽  
Early Development ◽  
Nuclear Periphery ◽  
Preimplantation Development ◽  
Lamin A ◽  
Positive Staining ◽  
Lamin B ◽  
Nuclear Lamins ◽  
Mouse Cells

The expression of nuclear lamins during mouse preimplantation development was studied by immunofluorescence, immunoblotting and immunoprecipitation. Two sera were used, specific either for lamin B or lamins A and C. Both sera gave a positive staining of the nuclear periphery throughout preimplantation development (fertilized eggs to late blastocysts). Immunoblots revealed that the three lamins were present in eggs and blastocysts. However, lamin A from eggs was found to have a higher apparent Mr than lamin A from blastocysts and other mouse cells. Using immunoprecipitation, synthesis of lamin A was detected in eggs while synthesis of lamin B was detected in 8-cell embryos and blastocysts, indicating that at least some of the lamins used during early development do not come from a store in the egg. These results are discussed in relation to the possible role of lamins during cell differentiation.

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