425 fig 4 proximity affects translocation frequencies

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from Parada and Misteli 2002, p. 425 Fig. 4. Proximity affects translocation frequencies. Chromosome territories that are close together in the interphase nucleus have a higher chance of undergoing reciprocal translocations than chromosomes that are far apart.
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from Chambeyron and Bickmore (2004) Genes and Dev. 18, 1119 Specific loci can be uniquely situated within their chromosome territory movement of expressed loci outside of chromosome territory induced expression of the HoxB cluster with Retinoic Acid in wild-type ES cells
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Question: How are genes/chromosome territories non-randomly distributed in the nucleus? Possible answer: Anchors Candidate “anchors” to position genes and chromosome territories in nuclei Nuclear Envelope Nucleolus Interchromatin Granule Clusters Transcription Factories Nuclear Bodies
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Review Article on “Anchoring” Cameron S. Osborne* and Christopher H. Eskiw (2008) Where Shall We Meet? A Role for Genome Organisation and Nuclear Sub- Compartments in Mediating Interchromosomal Interactions Journal of Cellular Biochemistry 104:1553 1561
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Nuclear Envelope Compartmentalisation at various levels is critical for regulation (regulation of factor concentrations within a volume) Keeping active regulatory factors inside or outside of the organelle Why important? Nuclear envelope implicated in numerous human diseases, including muscular dystrophy
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TEM of cell nucleus MBC 8-71
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Nuclear Envelope Organisation Pair of membranes-- inner and outer nuclear membranes (INM, ONM) Membranes periodically interrupted by nuclear pore complexes (NPC) large macromolecular assemblies that form aqueous gated channels that mediate regulated transport of macromolecules INM and ONM are connected at periphery of the NPC ONM is continuous with endoplasmic reticulum (ER) ribosomes on the cytoplasmic face of the ONM INM is enriched in unique proteins, which maintain associations with the underlying chromatin
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Organisation of the Nuclear Envelope from Burke and Stewart (2002) Nature Reviews Mol Cell Biol. 3, 575. Lamins ribosomes Figure 1 | Organization of the nuclear envelope. a | Electron micrographs of purified rat liver nuclear envelopes (NEs). The outer and inner nuclear membranes (ONM and INM, respectively) are clearly visible. Junctions between the ONM and INM are present at nuclear pores (arrows). The arrowheads in the main image indicate immunogold localization of lamins to the nuclear (inner) face of the INM. In the insert, the arrowhead indicates ribosomes that are attached to the cytoplasmic (outer) face of the ONM.
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Nuclear Lamina Regular lattice of specialised intermediate filaments (IFs) Important for the structural integrity of the nuclear envelope Composition: A-type and B-type lamins Central helical rod domain, self-assemble into parallel coiled-coil homodimers 2 types of genes: A-type gene codes for lamin A and lamin C, through alternative splicing of this developmentally regulated gene B-type lamin genes , LMNB1 and LMNB2, code for lamin B1, lamin B2
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Bridge between nucleus and cytoplasm UNCs and Nesprin Nesprin amongst the largest proteins in the cell (7,000-8,000 residues (1 MDa) Nesprin
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