PML bodies associate specifically with the MHC gene cluster in interphase nuclei

Promyelocytic leukemia (PML) bodies are nuclear multi-protein domains. The observations that viruses transcribe their genomes adjacent to PML bodies and that nascent RNA accumulates at their periphery suggest that PML bodies function in transcription. We have used immuno-FISH in primary human fibroblasts to determine the 3D spatial organisation of gene-rich and gene-poor chromosomal regions relative to PML bodies. We find a highly non-random association of the gene-rich major histocompatibilty complex (MHC) on chromosome 6 with PML bodies. This association is specific for the centromeric end of the MHC and extends over a genomic region of at least 1.6 megabases. We also show that PML association is maintained when a subsection of this region is integrated into another chromosomal location. This is the first demonstration that PML bodies have specific chromosomal associations and supports a model for PML bodies as part of a functional nuclear compartment.

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Ring chromosome 6 and i(17q−) in a patient with acute promyelocytic leukemia

Cancer Genetics and Cytogenetics ◽

10.1016/0165-4608(88)90272-5 ◽

1988 ◽

Vol 34 (2) ◽

pp. 273-276 ◽

Cited By ~ 1

Author(s):

Stephen J. Russell ◽

Helen Walker ◽

Francis J. Giles ◽

Anthony H. Goldstone

Keyword(s):

Acute Promyelocytic Leukemia ◽

Ring Chromosome ◽

Promyelocytic Leukemia ◽

Chromosome 6 ◽

Ring Chromosome 6

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The genomic organization of the region containing the Drosophila melanogaster rpL7a (Surf-3) gene differs from those of the mammalian and avian Surfeit loci.

Molecular and Cellular Biology ◽

10.1128/mcb.15.5.2367 ◽

1995 ◽

Vol 15 (5) ◽

pp. 2367-2373 ◽

Cited By ~ 12

Author(s):

N Armes ◽

M Fried

Keyword(s):

Drosophila Melanogaster ◽

Gene Cluster ◽

Ribosomal Protein Gene ◽

Single Copy ◽

Gene Organization ◽

Genomic Region ◽

Divergent Evolution ◽

Close Proximity ◽

Rapid Amplification ◽

Rna Blots

The Surf-3 gene of the unusually tight mouse Surfeit locus gene cluster has been identified as the highly conserved ribosomal protein gene L7a (rpL7a). The topography and juxtaposition of the Surfeit locus genes are conserved for the 600 million years of divergent evolution between mammals and birds. This suggests cis interaction and/or coregulation of the genes and suggests that, within this locus, gene organization plays an important role in gene expression. The further evolutionary conservation of the organization of the Surfeit locus was investigated. A cDNA encoding the Drosophila melanogaster homolog of the Surf-3/rpL7a gene was cloned, was shown to be present as a single copy, and was expressed constitutively at high levels throughout development. Genomic cosmid clones encompassing the gene and its surrounding DNA were isolated. The gene was determined to have five introns, of which two were located in the 5' untranslated region of the gene. The remaining three introns had splice sites at positions equivalent to those found in the Surf-3/rpL7a mammalian homologs. S1 analysis and 5' rapid amplification of cDNA ends both confirmed the start of transcription to occur in a polypyrimidine tract in the absence of a TATA box in the promoter. The genomic region around the Surf-3/rpL7a gene was analyzed by low-stringency hybridization with murine Surfeit gene probes, by partial sequence analysis, and by hybridization of fragments to Northern (RNA) blots. No homologs of other members of the Surfeit gene cluster were detected in close proximity to the D. melanogaster Surf-3/rpL7a gene. However, a gene which was detected directly 3' to the Surf-3/rpL7a gene was shown to encode a homolog of a mammalian serine-pyruvate aminotransferase.

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Molecular Characterization of the Leucine Cluster in Buchnera sp. Strain PSY, a Primary Endosymbiont of the Aphid Pemphigus spyrothecae

Applied and Environmental Microbiology ◽

10.1128/aem.68.5.2572-2575.2002 ◽

2002 ◽

Vol 68 (5) ◽

pp. 2572-2575 ◽

Cited By ~ 6

Author(s):

Beatriz Sabater-Muñoz ◽

Laura Gómez-Valero ◽

Roeland C. H. J. van Ham ◽

Francisco J. Silva ◽

Amparo Latorre

Keyword(s):

Gene Cluster ◽

Molecular Characterization ◽

Chromosomal Location ◽

Pemphigus Spyrothecae

ABSTRACT Buchnera strains from most aphid subfamilies studied to date have been found to carry the leucine gene cluster (leuA, -B, -C, and -D) on a plasmid, an organization unique among bacteria. Here, however, we demonstrate a classical chromosomal location of the cluster in Buchnera sp. strain PSY from the aphid Pemphigus spyrothecae (subfamily Pemphiginae). The genes that flank leuABCD in Buchnera sp. strain PSY appear to be adjacent in the genome of Buchnera sp. strain APS, a strain carrying a leucine plasmid. We propose that the presence of a leucine plasmid predates the diversification of symbiotic Buchnera and that the chromosomal location observed in Buchnera sp. strain PSY arose by a transfer of the leucine genes from a plasmid to the chromosome.

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Altered chromosome 6 in immortal human fibroblasts

Molecular and Cellular Biology ◽

10.1128/mcb.12.5.2273-2281.1992 ◽

1992 ◽

Vol 12 (5) ◽

pp. 2273-2281

Author(s):

K Hubbard-Smith ◽

P Patsalis ◽

J R Pardinas ◽

K K Jha ◽

A S Henderson ◽

...

Keyword(s):

Cell Lines ◽

Human Fibroblasts ◽

Rare Event ◽

Simian Virus 40 ◽

Simian Virus ◽

Chromosome 6 ◽

Karyotypic Analysis ◽

Diploid Fibroblasts ◽

Human Diploid Fibroblasts ◽

Immortal Cells

Human diploid fibroblasts have a limited life span in vitro, and spontaneous immortalization is an extremely rare event. We have used transformation of human diploid fibroblasts by an origin-defective simian virus 40 genome to develop series of genetically matched immortal cell lines to analyze immortalization. Comparison of a preimmortal transformant (SVtsA/HF-A) with its uncloned and cloned immortalized derivatives (AR5 and HAL) has failed to reveal any major alteration involving the simian virus 40 genome. Karyotypic analysis, however, demonstrated that all of the immortal cell lines in this series have alterations of chromosome 6 involving loss of the portion distal to 6q21. The karyotypic analysis was corroborated by DNA analyses. Southern analysis demonstrated that only one copy of three proto-oncogene loci (ros1, c-myb, and mas1) on 6q was retained in immortal cells. Polymerase chain reaction analysis of the microsatellite polymorphism at 6q22 (D6S87) showed loss of heterozygosity. In addition, elevated expression of c-myb (6q22-23) was observed. We hypothesize that the region at and/or distal to 6q21 plays a role in immortalization, consistent with the presence of a growth suppressor gene.

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Chromosomes exhibit preferential positioning in nuclei of quiescent human cells

Journal of Cell Science ◽

10.1242/jcs.112.4.525 ◽

1999 ◽

Vol 112 (4) ◽

pp. 525-535 ◽

Cited By ~ 3

Author(s):

R.G. Nagele ◽

T. Freeman ◽

L. McMorrow ◽

Z. Thomson ◽

K. Kitson-Wind ◽

...

Keyword(s):

Human Fibroblasts ◽

Dna Probes ◽

Human Cells ◽

Reference Points ◽

Chromosome X ◽

Interphase Nuclei ◽

Interphase Chromosome ◽

Chromosome Topology ◽

Spatial Positioning ◽

Diploid Cells

The relative spatial positioning of chromosomes 7, 8, 16, X and Y was examined in nuclei of quiescent (noncycling) diploid and triploid human fibroblasts using fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes and digital imaging. In quiescent diploid cells, interhomolog distances and chromosome homolog position maps revealed a nonrandom, preferential topology for chromosomes 7, 8 and 16, whereas chromosome X approximated a more random distribution. Variations in the orientation of nuclei on the culture substratum tended to hinder detection of an ordered chromosome topology at interphase by biasing homolog position maps towards random distributions. Using two chromosome X homologs as reference points in triploid cells (karyotype = 69, XXY), the intranuclear location of chromosome Y was found to be predictable within remarkably narrow spatial limits. Dual-FISH with various combinations of chromosome-specific DNA probes and contrasting fluorochromes was used to identify adjacent chromosomes in mitotic rosettes and test whether they are similarly positioned in interphase nuclei. From among the combinations tested, chromosomes 8 and 11 were found to be closely apposed in most mitotic rosettes and interphase nuclei. Overall, results suggest the existence of an ordered interphase chromosome topology in quiescent human cells in which at least some chromosome homologs exhibit a preferred relative intranuclear location that may correspond to the observed spatial order of chromosomes in rosettes of mitotic cells.

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Murine Hox-1.7 homeo-box gene: cloning, chromosomal location, and expression.

Molecular and Cellular Biology ◽

10.1128/mcb.7.10.3836 ◽

1987 ◽

Vol 7 (10) ◽

pp. 3836-3841 ◽

Cited By ~ 46

Author(s):

M R Rubin ◽

W King ◽

L E Toth ◽

I S Sawczuk ◽

M S Levine ◽

...

Keyword(s):

Chromosomal Location ◽

Inbred Mouse ◽

Distribution Patterns ◽

Mouse Strains ◽

Chromosome 6 ◽

Somatic Cell Hybrids ◽

Major Site ◽

Homeo Box ◽

Length Polymorphisms ◽

F9 Teratocarcinoma

A new murine homeo-box, called Hox-1.7, has been identified in a rare cDNA from F9 teratocarcinoma stem cells. The Hox-1.7 homeo-box is 68 and 72% homologous to the Drosophila antennapedia (Antp) and iab-7 homeo-boxes, respectively. A major 2.5-kilobase transcript and several minor transcripts were detected by Northern blot (RNA blot) analysis in adult tissues as well as in midgestational embryos. The posterior spinal cord was found to be a major site of Hox-1.7 expression in 12.5-day-old embryos. Somatic cell hybrids were used to map the Hox-1.7 gene to mouse chromosome 6. Restriction fragment length polymorphisms associated with either the Hox-1.7 gene or the previously known Hox-1 complex were identified. Their distribution patterns in recombinant inbred mouse strains were used to determine the linkage between the two loci as well as to other loci on chromosome 6. This maps Hox-1 and Hox-1.7 close to two mouse loci that affect morphogenesis, postaxial hemimelia (px) and hypodactyly (Hd).

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Distribution of ABL and BCR Genes in Cell Nuclei of Normal and Irradiated Lymphocytes

Blood ◽

10.1182/blood.v89.12.4537 ◽

1997 ◽

Vol 89 (12) ◽

pp. 4537-4545 ◽

Cited By ~ 66

Author(s):

S. Kozubek ◽

E. Lukášová ◽

L. Rýznar ◽

M. Kozubek ◽

A. Lišková ◽

...

Keyword(s):

Chromatin Structure ◽

Human Fibroblasts ◽

Physical Distance ◽

Gene Arrangement ◽

Cell Nuclei ◽

Interphase Nuclei ◽

Γ Radiation ◽

Shortest Distance ◽

G0 Phase

Abstract Using dual-color fluorescence in situ hybridization (FISH) combined with two-dimensional (2D) image analysis, the locations of ABL and BCR genes in cell nuclei were studied. The center of nucleus-to-gene and mutual distances of ABL and BCR genes in interphase nuclei of nonstimulated and stimulated lymphocytes as well as in lymphocytes stimulated after irradiation were determined. We found that, after stimulation, the ABL and BCR genes move towards the membrane, their mutual distances increase, and the shortest distance between heterologous ABL and BCR genes increases. The distribution of the shortest distances between ABL and BCR genes in the G0 phase of lymphocytes corresponds to the theoretical distribution calculated by the Monte-Carlo simulation. Interestingly, the shortest ABL-BCR distances in G1 and S(G2 ) nuclei are greater in experiment as compared with theory. This result suggests the existence of a certain regularity in the gene arrangement in the G1 and S(G2 ) nuclei that keeps ABL and BCR genes at longer than random distances. On the other hand, in about 2% to 8% of lymphocytes, the ABL and BCR genes are very close to each other (the distance is less than ∼0.2 to 0.3 μm). For comparison, we studied another pair of genes, c-MYC and IgH, that are critical for the induction of t(8; 14) translocation that occurs in the Burkitt's lymphoma. We found that in about 8% of lymphocytes, c-MYC and IgH are very close to each other. Similar results were obtained for human fibroblasts. γ-Radiation leads to substantial changes in the chromatin structure of stimulated lymphocytes: ABL and BCR genes are shifted to the nuclear center, and mutual ABL-BCR distances become much shorter in the G1 and S(G2 ) nuclei. Therefore, we hypothesize that the changes of chromatin structure in the irradiated lymphocytes might increase the probability of a translocation during G1 and S(G2 ) stages of the cell cycle. The fact that the genes involved in the t(8; 14) translocation are also located close together in a certain fraction of cells substantiates the hypothesis that physical distance plays an important role in the processes leading to the translocations that are responsible for oncogenic transformation of cells.

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