Distinctive nuclear organisation of centromeres and regions involved in pluripotency in human embryonic stem cells
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It is concluded that hES cell nuclei have a distinct nuclear architecture, especially at loci involved in maintaining pluripotency, which provides a framework within which other large-scale chromatin changes that may accompany differentiation can be considered.Abstract:
Nuclear organisation is thought to be important in regulating gene expression. Here we investigate whether human embryonic stem cells (hES) have a particular nuclear organisation, which could be important for maintaining their pluripotent state. We found that whereas the nuclei of hES cells have a general gene-density-related radial organisation of chromosomes, as is seen in differentiated cells, there are also distinctive localisations for chromosome regions and gene loci with a role in pluripotency. Chromosome 12p, a region of the human genome that contains clustered pluripotency genes including NANOG, has a more central nuclear localisation in ES cells than in differentiated cells. On chromosome 6p we find no overall change in nuclear chromosome position, but instead we detect a relocalisation of the OCT4 locus, to a position outside its chromosome territory. There is also a smaller proportion of centromeres located close to the nuclear periphery in hES cells compared to differentiated cells. We conclude that hES cell nuclei have a distinct nuclear architecture, especially at loci involved in maintaining pluripotency. Understanding this level of hES cell biology provides a framework within which other large-scale chromatin changes that may accompany differentiation can be considered.read more
Citations
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Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis
TL;DR: It is proposed that the effects of linear and spatial organization of gene loci on gene regulation are linked through TAD architecture, and that mitosis is critical for establishing nuclear topologies during cellular differentiation.
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Severe Progressive Autism Associated with Two de novo Changes: A 2.6-Mb 2q31.1 Deletion and a Balanced t(14;21)(q21.1;p11.2) Translocation with Long-Range Epigenetic Silencing of LRFN5 Expression
Diederik R.H. de Bruijn,A.H.A. van Dijk,R. Pfundt,Alexander Hoischen,Gerard Merkx,Gyri Aasland Gradek,Helle Lybæk,Asbjørg Stray-Pedersen,H.G. Brunner,Gunnar Houge +9 more
TL;DR: It is shown that translocations may influence gene expression more than 2 Mb away from the translocation breakpoint, and speculated that dysregulation of LRFN5, a postsynaptic density-associated gene, may contribute to the patient’s autism, even though 2 other patients with 14q13.2q21.3 deletions that included L RFN5 were not autistic.
Journal ArticleDOI
The nuclear periphery of embryonic stem cells is a transcriptionally permissive and repressive compartment
Li Luo,Katherine L. Gassman,Lydia M. Petell,Christian L. Wilson,Joerg Bewersdorf,Lindsay S. Shopland +5 more
TL;DR: In this article, the authors measured the nuclear distributions of genes in undifferentiated mouse ESCs according to epigenetic state and transcriptional activity and found that trimethyl histone H3 lysine 27 (H3K27-Me3), which marks repressed gene promoters, is enriched at the ESC nuclear periphery.
Journal Article
The nuclear periphery of embryonic stem cells is a transcriptionally permissive and repressive compartment
Li Luo,Katherine L. Gassman,Lydia M. Petell,Christian L. Wilson,Joerg Bewersdorf,Lindsay S. Shopland +5 more
TL;DR: It is found that trimethyl histone H3 lysine 27 (H3K27-Me3), which marks repressed gene promoters, is enriched at the ESC nuclear periphery, a compartment that represses some but not all associated genes and accumulates facultative heterochromatin in differentiated cells.
Journal ArticleDOI
Characterization of human UTF1, a chromatin-associated protein with repressor activity expressed in pluripotent cells.
TL;DR: It is shown with localization, subnuclear fractionation, and strip-FRAP analyses that human UTF1 is a tightly DNA-associated protein with transcriptional repressor activity and it is identified as a pluripotency-associated chromatin component with core histone-like characteristics.
References
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James A. Thomson,Joseph Itskovitz-Eldor,Sander S. Shapiro,Michelle A. Waknitz,Swiergiel Jennifer J,Vivienne S. Marshall,Jeffrey M. Jones +6 more
TL;DR: Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages.
Journal ArticleDOI
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Chunhui Xu,Margaret S. Inokuma,Jerrod Denham,Kathaleen Golds,Pratima Kundu,Joseph D. Gold,Melissa K. Carpenter +6 more
TL;DR: A successful feeder-free hES culture system in which undifferentiated cells can be maintained for at least 130 population doublings and are suitable for scaleup production is demonstrated.
Journal ArticleDOI
"Stemness": Transcriptional Profiling of Embryonic and Adult Stem Cells
TL;DR: The transcriptional profiles of mouse embryonic, neural, and hematopoietic stem cells were compared to define a genetic program for stem cells and provide a foundation for a more detailed understanding of stem cell biology.
Journal ArticleDOI
Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells
Jonathan S. Draper,Kath Smith,Paul J. Gokhale,Harry Moore,Edna Maltby,Julie A. Johnson,Lorraine F. Meisner,Thomas P. Zwaka,James A. Thomson,Peter W. Andrews +9 more
TL;DR: It is suggested that increased dosage of chromosome 17q and 12 gene(s) provides a selective advantage for the propagation of undifferentiated hES cells in transplantation therapies in which the use of aneuploid cells could be detrimental.
Journal ArticleDOI
Differences in the localization and morphology of chromosomes in the human nucleus
TL;DR: It is demonstrated that the distribution of genomic sequences between chromosomes has implications for nuclear structure and the findings are discussed in relation to a model of the human nucleus that is functionally compartmentalized.
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