A cloned repeated DNA sequence in human chromosome heteromorphisms

Gosden, John R.; Lawrie, Sandra S.; Cooke, Howard J.

doi:10.1159/000131549

Cited by 52 publications

(21 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…47 . Therefore, for an ICF patient with a given genotype, the size of the 1qh and 16qh heterochromatins, which corresponds to the amount of satellite DNA, 48 could influence the severity of the phenotype.…”

Section: Discussionmentioning

confidence: 99%

Subcellular distribution of HP1 proteins is altered in ICF syndrome

et al. 2004

View full text Add to dashboard Cite

The Immunodeficiency, Centromeric instability, and Facial (ICF) syndrome is a rare autosomal recessive disorder that results from mutations in the DNMT3B gene, encoding a DNA-methyltransferase that acts on GC-rich satellite DNAs. This syndrome is characterized by immunodeficiency, facial dysmorphy, mental retardation of variable severity and chromosomal abnormalities that essentially involve juxtacentromeric heterochromatin of chromosomes 1 and 16. These abnormalities demonstrate that hypomethylation of satellite DNA can induce alterations in the structure of heterochromatin. In order to investigate the effect of DNA hypomethylation on heterochromatin organization, we analyzed the in vivo distribution of HP1 proteins, essential components of heterochromatin, in three ICF patients. We observed that, in a large proportion of ICF G2 nuclei, all HP1 isoforms show an aberrant signal concentrated into a prominent bright focus that co-localizes with the undercondensed 1qh or 16qh heterochromatin. We found that SP100, SUMO-1 and other proteins from the promyelocytic leukemia nuclear bodies (NBs) form a large body that co-localizes with the HP1 signal. This is the first description of altered nuclear distribution of HP1 proteins in the constitutional ICF syndrome. Our results show that satellite DNA hypomethylation does not prevent HP1 proteins from associating with heterochromatin. They suggest that, at G2 phase, HP1 proteins are involved in the heterochromatin condensation and may therefore remain concentrated at these sites until the condensation is complete. They also indicate that proteins from the NB could play a role in this process. Finally, satellite DNA length polymorphism could affect the efficiency of heterochromatin condensation and thus contribute to the variability of the ICF phenotype.

show abstract

Section: Discussionmentioning

confidence: 99%

Subcellular distribution of HP1 proteins is altered in ICF syndrome

et al. 2004

View full text Add to dashboard Cite

show abstract

“…merit regions of other chromosomes such as chromosome 9 in case of lc and chromosome 2 in case of 18c indicated some cross-hybridization to related sequences in the constitutive heterochromatin of these other chromosomes [3,27,311. Generally these minor signals were easily distinguished on the basis of intensity.…”

Section: Resultsmentioning

confidence: 99%

“…Cloned variants of the alphoid repeats such as 18c are not optimal as "chromosome-specific" probes since these sequences have some homology to repeated DNAs on essentially all human centromeres and are variants of a consensus sequence [3, 21-23, 31, 4111; lc also has been reported to reveal minor hybridization sites on several other chromosomes [27]. In double hybridization expetiments performed under a variety of less stringent hybridization conditions (not shown) we found, however, that lc was still largely confined to lq12, whereas 18c hybridized to the centromeric regions of most chromosomes [3].…”

Section: Discussionmentioning

confidence: 99%

“…It should be noted that the stringency of hybridization and posthybridization washes is crucial for detection of "chromosome specific" labeling by lc and 18c DNA probes. These DNA inserts will hybridize to several chromosomes in addition to chromosomes 1 and 18 with reduced formamide concentrations, e.g., at 40% formamide [3,27,311. Hybridization mixtures with formamide concentrations higher than 60%, or posthybridization washes at higher temperatures, yielded weaker but not significantly more specific signals.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Rapid interphase and metaphase assessment of specific chromosomal changes in neuroectodermal tumor cells by in situ hybridization with chemically modified DNA probes

Cremer

Tesin

Hopman

et al. 1988

Experimental Cell Research

152

View full text Add to dashboard Cite

Repeated DNAs from the constitutive heterochromatin of human chromosomes 1 and 18 were used as probes in nonradioactive in situ hybridization experiments to define specific numerical and structural chromosome aberrations in three human glioma cell lines and one neuroblastoma cell line. The number of spots detected in interphase nuclei of these tumor cell lines and in normal diploid nuclei correlated well with metaphase counts of chromosomes specifically labeled by in situ hybridization. Rapid and reliable assessments of aneuploid chromosome numbers in tumor lines in double hybridization experiments were achieved, and rare cells with bizarre phenotype and chromosome constitution could be evaluated in a given tumor cell population. Even with suboptimal or rare chromosome spreads specific chromosome aberrations were delineated. As more extensive probe sets become available this approach will become increasingly powerful for uncovering various genetic alterations and their progression in tumor cells. 0 1988 Academic Press. Inc.Specific chromosome aberrations are thought to be important in the development of malignant human gliomas. However, several groups have noted that adequate chromosome analyses of both primary cultures and of solid glioma samples are problematic [ 1, 21. These difficulties are generally encountered in all cytogenetic analyses of solid tumors; many tumor preparations do not contain sufficient numbers of well-spread and banded metaphase cells, and a large number of mitotic cells within solid tumors are inaccessible for analysis. With such small samples of mitotic cells it is difficult to determine if a chromosomal pattern is representative of the whole tumor cell population. Thus specific numerical and structural aberrations in a given tumor type are difficult to confirm on a broad scale, and rare aberrant cells with special malignant propensities may also be overlooked. Furthermore the analysis of complex chromosome changes in very aneuploid cells requires the detailed attention of highly skilled observers. Even when these time consuming analyses are performed by experienced cytogeneticists, it is difficult to pinpoint chromosomal breakpoints and segments involved in duplication, deletion, or translocation [l].We are attempting to develop procedures and DNA probe sets for visualization of specific numerical and structural aberrations in tumor cells. The detection of chromosome abnormalities in interphase nuclei, an approach termed "interphase cytogenetics"[3], appears to be a useful addition to the classical metaphase analysis. The examination of numerical aberrations in interphase nuclei can yield ' TO whom reprint requests should be addressed 199

show abstract

“…The hybridization to other chromosomes such as 9 and 16 is much less and not related to the size of the C-band. Hybridization to the Y occurs only in some individuals and a very small amount reassociates with chromosome 15 (GosDEN et al 1981). The hybridization pattern of total satellite III is not at all related to that of this sequence isolated from it.…”

mentioning

confidence: 88%

On the Heterogeneity of Heterochromatin

Rocchi¹

1982

Caryologia

View full text Add to dashboard Cite

A cloned repeated DNA sequence in human chromosome heteromorphisms

Cited by 52 publications

References 7 publications

Subcellular distribution of HP1 proteins is altered in ICF syndrome

Subcellular distribution of HP1 proteins is altered in ICF syndrome

Rapid interphase and metaphase assessment of specific chromosomal changes in neuroectodermal tumor cells by in situ hybridization with chemically modified DNA probes

On the Heterogeneity of Heterochromatin

Contact Info

Product

Resources

About