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  • 1
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2005
    In:  Genes & Development Vol. 19, No. 10 ( 2005-05-15), p. 1188-1198
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 19, No. 10 ( 2005-05-15), p. 1188-1198
    Abstract: Although the spatial location of genes within the nucleus has been implicated in their transcriptional status, little is known about the dynamics of gene location that accompany large-scale changes in gene expression. The mating of haploid yeast Saccharomyces cerevisiae is accompanied by a large-scale change in transcription and developmental program. We examined changes in nuclear organization that accompany stimulus by the mating pheromone α factor and found that most α-factor-induced genes become associated with components of the nuclear envelope. The myosin-like protein Mlp1, which has been implicated in mRNA export, was further shown to exhibit RNA dependence in its association with α-factor-induced genes. High-resolution mapping of association of chromosome III with Mlp1 revealed α-factor-dependent determinants of nuclear pore association, including origins of replication, specific intergenic regions, and the 3′ ends of transcriptionally activated genes. Taken together, these results reveal RNA- and DNA-dependent determinants of nuclear organization as well as a detailed picture of how an entire chromosome alters its spatial conformation in response to a developmental cue.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2005
    detail.hit.zdb_id: 1467414-2
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Cold Spring Harbor Laboratory ; 2008
    In:  Genes & Development Vol. 22, No. 5 ( 2008-03-01), p. 627-639
    In: Genes & Development, Cold Spring Harbor Laboratory, Vol. 22, No. 5 ( 2008-03-01), p. 627-639
    Abstract: The nuclear localization of genes is intimately tied to their transcriptional status in Saccharomyces cerevisiae , with populations of both active and silent genes interacting with components of the nuclear envelope. We investigated the relationship between the mammalian nuclear pore and the human genome by generating high-resolution, chromosome-wide binding maps of human nucleoporin 93 (Nup93) in the presence and absence of a potent histone deacetylase inhibitor (HDACI). Here, we report extensive genomic reorganization with respect to the nuclear pore following HDACI treatment, including the recruitment of promoter regions, euchromatin-rich domains, and differentially expressed genes. In addition to biochemical mapping, we visually demonstrate the physical relocalization of several genomic loci with respect to the nuclear periphery. Our studies show that inhibiting HDACs leads to significant changes in genomic organization, recruiting regions of transcriptional regulation to mammalian nuclear pore complexes.
    Type of Medium: Online Resource
    ISSN: 0890-9369 , 1549-5477
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2008
    detail.hit.zdb_id: 1467414-2
    SSG: 12
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    American Physiological Society ; 2008
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 294, No. 6 ( 2008-06), p. H2864-H2870
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 294, No. 6 ( 2008-06), p. H2864-H2870
    Abstract: Atherosclerosis is an inflammatory disease involving the accumulation of macrophages in the intima. Wnt5a is a noncanonical member of the Wnt family of secreted glycoproteins. Recently, human macrophages have been shown to express Wnt5a upon stimulation with bacterial pathogens in vitro and in granulomatous lesions in the lung of Mycobacterium tuberculosis-infected patients. Wnt5a expression has also been liked to Toll-like receptor-4 (TLR-4), an innate immune receptor implicated in atherosclerosis. These observations, along with the fact that Wnt5a is involved in cell migration and proliferation, led us to postulate that Wnt5a plays a role in atherosclerosis. To investigate this hypothesis, we characterized Wnt5a expression in murine and human atherosclerotic lesions. Tissue sections derived from the aortic sinus to the aortic arch of apolipoprotein E-deficient mice and sections derived from the carotid arteries of patients undergoing endarterectomy were subjected to immunohistochemical analysis. All samples were found to be positive for Wnt5a with predominant staining in the areas of macrophage accumulation within the intima. In parallel, we probed for the presence of TLR-4 and found coincident TLR-4 and Wnt5a expression. For both the Wnt5a and TLR-4 staining, consecutive tissue sections treated with an isotype- and species-matched Ig served as a negative control and exhibited little, if any, reactivity. Quantitative RT-PCR revealed that Wnt5a mRNA expression in RAW264.7 murine macrophages can be induced by stimulation with LPS, a known ligand for TLR-4. Combined, these findings demonstrate for the first time Wnt5a expression in human and murine atherosclerotic lesions and suggest that cross talk between TLR-4 and Wnt5a is operative in atherosclerosis.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    RVK:
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2008
    detail.hit.zdb_id: 1477308-9
    SSG: 12
    Location Call Number Limitation Availability
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