LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article ; Online: A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence.

    Kumaran, R Ileng / Spector, David L

    The Journal of cell biology

    2008  Volume 180, Issue 1, Page(s) 51–65

    Abstract: The peripheral nuclear lamina, which is largely but not entirely associated with inactive chromatin, is considered to be an important determinant of nuclear structure and gene expression. We present here an inducible system to target a genetic locus to ... ...

    Abstract The peripheral nuclear lamina, which is largely but not entirely associated with inactive chromatin, is considered to be an important determinant of nuclear structure and gene expression. We present here an inducible system to target a genetic locus to the nuclear lamina in living mammalian cells. Using three-dimensional time-lapse microscopy, we determined that targeting of the locus requires passage through mitosis. Once targeted, the locus remains anchored to the nuclear periphery in interphase as well as in daughter cells after passage through a subsequent mitosis. Upon transcriptional induction, components of the gene expression machinery are recruited to the targeted locus, and we visualized nascent transcripts at the nuclear periphery. The kinetics of transcriptional induction at the nuclear lamina is similar to that observed at an internal nuclear region. This new cell system provides a powerful approach to study the dynamics of gene function at the nuclear periphery in living cells.
    MeSH term(s) Cell Line ; Chromosomes/physiology ; Gene Expression Regulation/physiology ; Humans ; Interphase ; Kinetics ; Lamins/analysis ; Lamins/metabolism ; Luminescent Proteins/analysis ; Mitosis/physiology ; Models, Genetic ; Nuclear Lamina/genetics ; Nuclear Lamina/metabolism ; Nuclear Lamina/ultrastructure ; Transcription, Genetic/physiology
    Chemical Substances Lamins ; Luminescent Proteins
    Language English
    Publishing date 2008-01-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.200706060
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ub I Zs.190: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Chromatin dynamics and gene positioning.

    Kumaran, R Ileng / Thakar, Rajika / Spector, David L

    Cell

    2008  Volume 132, Issue 6, Page(s) 929–934

    Abstract: The mammalian cell nucleus provides a landscape where genes are regulated through their organization and association with freely diffusing proteins and nuclear domains. In many cases, specific genes are highly dynamic, and the principles governing their ... ...

    Abstract The mammalian cell nucleus provides a landscape where genes are regulated through their organization and association with freely diffusing proteins and nuclear domains. In many cases, specific genes are highly dynamic, and the principles governing their movements and interchromosomal interactions are currently under intensive study. Recent investigations have implicated actin and myosin in chromatin dynamics and gene expression. Here, we discuss our current understanding of the dynamics of the interphase genome and how it impacts nuclear organization and gene activity.
    MeSH term(s) Animals ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; Chromatin/metabolism ; Chromosomes/metabolism ; Gene Expression Regulation ; Humans ; Interphase
    Chemical Substances Chromatin
    Language English
    Publishing date 2008-03-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2008.03.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1167: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 58: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Lamin A/C haploinsufficiency modulates the differentiation potential of mouse embryonic stem cells.

    Poonam Sehgal / Pankaj Chaturvedi / R Ileng Kumaran / Satish Kumar / Veena K Parnaik

    PLoS ONE, Vol 8, Iss 2, p e

    2013  Volume 57891

    Abstract: Background Lamins are structural proteins that are the major determinants of nuclear architecture and play important roles in various nuclear functions including gene regulation and cell differentiation. Mutations in the human lamin A gene cause a ... ...

    Abstract Background Lamins are structural proteins that are the major determinants of nuclear architecture and play important roles in various nuclear functions including gene regulation and cell differentiation. Mutations in the human lamin A gene cause a spectrum of genetic diseases that affect specific tissues. Most available mouse models for laminopathies recapitulate disease symptoms for muscle diseases and progerias. However, loss of human lamin A/C also has highly deleterious effects on fetal development. Hence it is important to understand the impact of lamin A/C expression levels on embryonic differentiation pathways. Methodology and principal findings We have investigated the differentiation potential of mouse embryonic stem cells containing reduced levels of lamin A/C by detailed lineage analysis of embryoid bodies derived from these cells by in vitro culture. We initially carried out a targeted disruption of one allele of the mouse lamin A/C gene (Lmna). Undifferentiated wild-type and Lmna(+/-) embryonic stem cells showed similar expression of pluripotency markers and cell cycle profiles. Upon spontaneous differentiation into embryoid bodies, markers for visceral endoderm such as α-fetoprotein were highly upregulated in haploinsufficient cells. However, neuronal markers such as β-III tubulin and nestin were downregulated. Furthermore, we observed a reduction in the commitment of Lmna(+/-) cells into the myogenic lineage, but no discernible effects on cardiac, adipocyte or osteocyte lineages. In the next series of experiments, we derived embryonic stem cell clones expressing lamin A/C short hairpin RNA and examined their differentiation potential. These cells expressed pluripotency markers and, upon differentiation, the expression of lineage-specific markers was altered as observed with Lmna(+/-) embryonic stem cells. Conclusions We have observed significant effects on embryonic stem cell differentiation to visceral endoderm, neuronal and myogenic lineages upon depletion of lamin A/C. Hence our results ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Lamin A/C haploinsufficiency modulates the differentiation potential of mouse embryonic stem cells.

    Sehgal, Poonam / Chaturvedi, Pankaj / Kumaran, R Ileng / Kumar, Satish / Parnaik, Veena K

    PloS one

    2013  Volume 8, Issue 2, Page(s) e57891

    Abstract: Background: Lamins are structural proteins that are the major determinants of nuclear architecture and play important roles in various nuclear functions including gene regulation and cell differentiation. Mutations in the human lamin A gene cause a ... ...

    Abstract Background: Lamins are structural proteins that are the major determinants of nuclear architecture and play important roles in various nuclear functions including gene regulation and cell differentiation. Mutations in the human lamin A gene cause a spectrum of genetic diseases that affect specific tissues. Most available mouse models for laminopathies recapitulate disease symptoms for muscle diseases and progerias. However, loss of human lamin A/C also has highly deleterious effects on fetal development. Hence it is important to understand the impact of lamin A/C expression levels on embryonic differentiation pathways.
    Methodology and principal findings: We have investigated the differentiation potential of mouse embryonic stem cells containing reduced levels of lamin A/C by detailed lineage analysis of embryoid bodies derived from these cells by in vitro culture. We initially carried out a targeted disruption of one allele of the mouse lamin A/C gene (Lmna). Undifferentiated wild-type and Lmna(+/-) embryonic stem cells showed similar expression of pluripotency markers and cell cycle profiles. Upon spontaneous differentiation into embryoid bodies, markers for visceral endoderm such as α-fetoprotein were highly upregulated in haploinsufficient cells. However, neuronal markers such as β-III tubulin and nestin were downregulated. Furthermore, we observed a reduction in the commitment of Lmna(+/-) cells into the myogenic lineage, but no discernible effects on cardiac, adipocyte or osteocyte lineages. In the next series of experiments, we derived embryonic stem cell clones expressing lamin A/C short hairpin RNA and examined their differentiation potential. These cells expressed pluripotency markers and, upon differentiation, the expression of lineage-specific markers was altered as observed with Lmna(+/-) embryonic stem cells.
    Conclusions: We have observed significant effects on embryonic stem cell differentiation to visceral endoderm, neuronal and myogenic lineages upon depletion of lamin A/C. Hence our results implicate lamin A/C level as an important determinant of lineage-specific differentiation during embryonic development.
    MeSH term(s) Animals ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; Down-Regulation ; Embryoid Bodies/metabolism ; Embryoid Bodies/physiology ; Embryonic Development/genetics ; Embryonic Development/physiology ; Embryonic Stem Cells/metabolism ; Embryonic Stem Cells/physiology ; Endoderm/metabolism ; Endoderm/physiology ; Gene Expression Regulation/genetics ; Haploinsufficiency ; Heterozygote ; Lamin Type A/genetics ; Lamin Type A/metabolism ; Mice ; Neurons/metabolism ; Neurons/physiology ; alpha-Fetoproteins/genetics ; alpha-Fetoproteins/metabolism
    Chemical Substances Lamin Type A ; alpha-Fetoproteins ; lamin C
    Language English
    Publishing date 2013-02-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0057891
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article: A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence

    Kumaran, R. Ileng / Spector, David L

    Journal of cell biology. 2008 Jan. 14, v. 180, no. 1

    2008  

    Abstract: The peripheral nuclear lamina, which is largely but not entirely associated with inactive chromatin, is considered to be an important determinant of nuclear structure and gene expression. We present here an inducible system to target a genetic locus to ... ...

    Abstract The peripheral nuclear lamina, which is largely but not entirely associated with inactive chromatin, is considered to be an important determinant of nuclear structure and gene expression. We present here an inducible system to target a genetic locus to the nuclear lamina in living mammalian cells. Using three-dimensional time-lapse microscopy, we determined that targeting of the locus requires passage through mitosis. Once targeted, the locus remains anchored to the nuclear periphery in interphase as well as in daughter cells after passage through a subsequent mitosis. Upon transcriptional induction, components of the gene expression machinery are recruited to the targeted locus, and we visualized nascent transcripts at the nuclear periphery. The kinetics of transcriptional induction at the nuclear lamina is similar to that observed at an internal nuclear region. This new cell system provides a powerful approach to study the dynamics of gene function at the nuclear periphery in living cells.
    Language English
    Dates of publication 2008-0114
    Size p. 51-65.
    Publishing place The Rockefeller University Press
    Document type Article
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

    In stock of ZB MED Bonn / Germany

    Z 56/32: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article: Lamin A/C speckles mediate spatial organization of splicing factor compartments and RNA polymerase II transcription.

    Kumaran, R Ileng / Muralikrishna, Bhattiprolu / Parnaik, Veena K

    The Journal of cell biology

    2002  Volume 159, Issue 5, Page(s) 783–793

    Abstract: 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 ...

    Abstract 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 alpha-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.
    MeSH term(s) Amanitins/pharmacology ; Antibodies, Monoclonal/metabolism ; Cell Compartmentation ; Cell Nucleus/chemistry ; Cell Nucleus/enzymology ; Cell Nucleus/metabolism ; Dichlororibofuranosylbenzimidazole/pharmacology ; Down-Regulation ; HeLa Cells ; Humans ; Kinetics ; Lamin Type A/genetics ; Lamin Type A/physiology ; Lamin Type A/ultrastructure ; Nuclear Proteins/analysis ; Nucleic Acid Synthesis Inhibitors/pharmacology ; RNA Polymerase II/antagonists & inhibitors ; RNA Polymerase II/metabolism ; RNA Splicing ; Recombinant Proteins/metabolism ; Transcription, Genetic ; Tumor Cells, Cultured
    Chemical Substances Amanitins ; Antibodies, Monoclonal ; Lamin Type A ; Nuclear Proteins ; Nucleic Acid Synthesis Inhibitors ; Recombinant Proteins ; lamin C ; Dichlororibofuranosylbenzimidazole (53-85-0) ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2002-12-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.200204149
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Ub I Zs.190: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Receptor-mediated delivery of engineered nucleases for genome modification.

    Chen, Zhong / Jaafar, Lahcen / Agyekum, Davies G / Xiao, Haiyan / Wade, Marlene F / Kumaran, R Ileng / Spector, David L / Bao, Gang / Porteus, Matthew H / Dynan, William S / Meiler, Steffen E

    Nucleic acids research

    2013  Volume 41, Issue 19, Page(s) e182

    Abstract: Engineered nucleases, which incise the genome at predetermined sites, have a number of laboratory and clinical applications. There is, however, a need for better methods for controlled intracellular delivery of nucleases. Here, we demonstrate a method ... ...

    Abstract Engineered nucleases, which incise the genome at predetermined sites, have a number of laboratory and clinical applications. There is, however, a need for better methods for controlled intracellular delivery of nucleases. Here, we demonstrate a method for ligand-mediated delivery of zinc finger nucleases (ZFN) proteins using transferrin receptor-mediated endocytosis. Uptake is rapid and efficient in established mammalian cell lines and in primary cells, including mouse and human hematopoietic stem-progenitor cell populations. In contrast to cDNA expression, ZFN protein levels decline rapidly following internalization, affording better temporal control of nuclease activity. We show that transferrin-mediated ZFN uptake leads to site-specific in situ cleavage of the target locus. Additionally, despite the much shorter duration of ZFN activity, the efficiency of gene correction approaches that seen with cDNA-mediated expression. The approach is flexible and general, with the potential for extension to other targeting ligands and nuclease architectures.
    MeSH term(s) Animals ; Cell Line ; Cells, Cultured ; DNA Cleavage ; Deoxyribonucleases/genetics ; Deoxyribonucleases/metabolism ; Endocytosis ; Genomics ; Humans ; Ligands ; Mice ; Protein Engineering ; Receptors, Transferrin/metabolism ; Recombinant Fusion Proteins/metabolism ; Targeted Gene Repair/methods ; Transferrin/genetics ; Transferrin/metabolism ; Zinc Fingers
    Chemical Substances Ligands ; Receptors, Transferrin ; Recombinant Fusion Proteins ; Transferrin ; Deoxyribonucleases (EC 3.1.-)
    Language English
    Publishing date 2013-08-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkt710
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1067: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top