Nuclear structure and gene activity in human differentiated cells
| Autor: | Eva Bártová, Hana Gajová, Stanislav Kozubek, Michal Kozubek, Pavla Jirsová, Emilie Lukášová, Magdalena Skalníková, Michael Hausmann, Irena Koutná, Alena Gaňová |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Nuclear gene
Heterochromatin Cellular differentiation Pair-rule gene HL-60 Cells Genes abl Biology Resting Phase Cell Cycle Retinoblastoma Protein Translocation Genetic Proto-Oncogene Proteins c-myc 03 medical and health sciences 0302 clinical medicine Structural Biology Gene cluster Tumor Cells Cultured Humans Gene Silencing Proto-Oncogene Proteins c-abl 10. No inequality In Situ Hybridization Fluorescence 030304 developmental biology Chromosome 13 Cell Nucleus Chromosomes Human X 0303 health sciences ABL Chromosomes Human Pair 13 Reverse Transcriptase Polymerase Chain Reaction Cell Membrane G1 Phase Cell Differentiation DNA Methylation Molecular biology eye diseases 030220 oncology & carcinogenesis Chromosome Territory Chromosomes Human Pair 8 |
| Zdroj: | Journal of Structural Biology. 139:76-89 |
| ISSN: | 1047-8477 |
| DOI: | 10.1016/s1047-8477(02)00560-9 |
| Popis: | The nuclear arrangement of the ABL, c-MYC, and RB1 genes was quantitatively investigated in human undifferentiated HL-60 cells and in a terminally differentiated population of human granulocytes. The ABL gene was expressed in both cell types, the c-MYC gene was active in HL-60 cells and down-regulated in granulocytes, and expression of the RB1 gene was undetectable in HL-60 cells but up-regulated in granulocytes. The distances of these genes to the nuclear center (membrane), to the center of the corresponding chromosome territory, and to the nearest centromere were determined. During granulopoesis, the majority of selected genetic structures were repositioned closer to the nuclear periphery. The nuclear reposition of the genes studied did not correlate with the changes of their expression. In both cell types, the c-MYC and RB1 genes were located at the periphery of the chromosome territories regardless of their activity. The centromeres of chromosomes 8 and 13 were always positioned more centrally within the chromosome territory than the studied genes. Close spatial proximity of the c-MYC and RB1 genes with centromeric heterochromatin, forming the chromocenters, correlated with gene activity, although the nearest chromocenter of the silenced RB1 gene did not involve centromeric heterochromatin of chromosome 13 where the given gene is localized. In addition, the role of heterochromatin in gene silencing was studied in retinoblastoma cells. In these differentiated tumor cells, one copy of the RB1 gene was positioned near the heterochromatic chromosome X, and reduced RB1 gene activity was observed. In the experiments presented here, we provide evidence that the regulation of gene activity during important cellular processes such as differentiation or carcinogenesis may be realized through heterochromatin-mediated gene silencing. |
| Databáze: | OpenAIRE |
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