Different patterns of gene silencing in position-effect variegation

Lloyd, Vett K.; Dyment, David A.; Sinclair, Donald A. R.; Grigliatti, Thomas A.

doi:10.1139/g03-070

Cited by 21 publications

(14 citation statements)

References 31 publications

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“…The other characteristics are probably the result of the loss of genetic material during the formation of the ring chromosome, although we cannot rule out the influence of changes in the chromatin architecture of the chromosome, which may result in a change of expression and could cause the silencing of adjacent genes [Zeng et al, 2002;Lloyd et al, 2003].…”

Section: Discussionmentioning

confidence: 96%

Clinical, Cytogenetic and Molecular Study in a Case of r(3) with 3p Deletion and Review of the Literature

Guilherme

Bragagnolo²,

Pellegrino³

et al. 2011

Cytogenet Genome Res

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Ring chromosome 3 is a rare abnormality with only 10 patients described in the literature. We report a patient with r(3) and ∼6-Mb distal 3p deletion. Single nucleotide polymorphism array, multiplex ligation-dependent probe amplification and fluorescence in situ hybridization techniques revealed that the ring was formed by a break in 3p26.1 and fusion with the subtelomeric region of 3q. The patient presents delayed psychomotor development, growth failure, minor anomalies and other features similar to patients with 3p monosomy. The analysis of 300 metaphase cells using G-banding and fluorescence in situ hybridization with centromeric probe revealed ring instability resulting in cells with secondary aberrations and with ring loss that could also be related to some phenotypic characteristics such as growth delay. This is the first patient with r(3) studied using molecular techniques that determined the exact breakpoints in order to establish a better karyotype-phenotype correlation.

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Section: Discussionmentioning

confidence: 96%

Clinical, Cytogenetic and Molecular Study in a Case of r(3) with 3p Deletion and Review of the Literature

Guilherme

Bragagnolo²,

Pellegrino³

et al. 2011

Cytogenet Genome Res

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“…Chromosomal rearrangements frequently lead to alteration of the gene's environment and this may be reflected in a change of expression. Despite the size of the deletion on 14q, the juxtaposition of the DNA from q-arm close to the inactive heterochromatin of the centromere and p-arm could cause silencing of adjacent genes [Grewal and Moazed, 2003;Lloyd et al, 2003]. Integrating at or near the centromere can cause position effect variegation (PEV) resulting in silencing of the genes in a fraction of the cells.…”

Section: Discussionmentioning

confidence: 99%

FISH‐mapping of telomeric 14q32 deletions: Search for the cause of seizures

Schlade-Bartusiak

Costa

Summers

et al. 2005

American J of Med Genetics Pt A

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Ring chromosome 14 is a rare cytogenetic disorder. Individuals with r(14) generally have developmental delay and seizures. Other features include hypotonia, microcephaly, mild facial dysmorphism, and retinal pigmentation. Most of these features are also found in patients with linear terminal deletions of chromosome 14, except for seizures and retinal abnormalities. The objective of the study was to determine if deletion of a specific chromosome region is a possible explanation for the occurrence of seizures in patients with ring chromosome 14. Patients diagnosed either with r(14) (six patients) or a deletion of distal 14q (three patients) were analyzed by FISH (fluorescence in situ hybridization) with BAC probes. We observed differences in the size of deletions in the studied group. In two r(14) patients, we did not detect any deletion; the four other patients had deletions of various sizes, ranging from 0.8 Mb to 5 Mb. Two linear deletions were 3.2 Mb and 5.3 Mb in length, respectively; the third case had an interstitial deletion that did not overlap with the others. The deleted regions in ring chromosomes showed overlap with those in the two linear terminal deletions. We conclude that there is unlikely to be a specific deleted locus in 14q32.3 that predisposes r(14) patients to seizures or retinal pigmentation. The cause is probably related to the formation of the ring itself and the effect this may have on local chromatin structure.

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“…Because white-opaque switching occurs spontaneously, reversibly, and at relatively high frequency, it has been suggested (21,41,42,46) that it may be the result of "position-effect variegation," a metastable change in the expression of a gene, mediated by a change in chromatin state effected by a neighboring silent region (12,20,28). This hypothesis was supported by the observation that the deacetylase inhibitor trichostatin A or deletion of the deacetylase gene HDA1 or RPD3 caused increases in the frequency of whiteopaque switching (21,46).…”

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confidence: 99%

TOS9 Regulates White-Opaque Switching in Candida albicans

et al. 2006

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In Candida albicans, the a1-␣2 complex represses white-opaque switching, as well as mating. Based upon the assumption that the a1-␣2 corepressor complex binds to the gene that regulates white-opaque switching, a chromatin immunoprecipitation-microarray analysis strategy was used to identify 52 genes that bound to the complex. One of these genes, TOS9, exhibited an expression pattern consistent with a "master switch gene." TOS9 was only expressed in opaque cells, and its gene product, Tos9p, localized to the nucleus. Deletion of the gene blocked cells in the white phase, misexpression in the white phase caused stable mass conversion of cells to the opaque state, and misexpression blocked temperature-induced mass conversion from the opaque state to the white state. A model was developed for the regulation of spontaneous switching between the opaque state and the white state that includes stochastic changes of Tos9p levels above and below a threshold that induce changes in the chromatin state of an as-yet-unidentified switching locus. TOS9 has also been referred to as EAP2 and WOR1.White-opaque switching was first observed in a strain of Candida albicans isolated from a fatal bloodstream infection (40). The switch affected the cellular phenotype (1, 41, 42), gene expression (24), and a variety of putative virulence traits (40, 41). It also conferred the capacity to colonize skin (23). An early analysis of clinical strains performed in 1986, however, revealed that only 8% underwent the switch (D. R. Soll, unpublished observation; 44). This observation was enigmatic, since all strains of C. albicans possessed opaque state-specific genes (33). In 2002, Miller and Johnson (31) provided not only an explanation for this enigma but also a role for the whiteopaque transition. They found that while an a/␣ laboratory strain could not switch, MTLa1 and MTL␣2 deletion derivatives of that strain, which were ␣ and a, respectively, could. They demonstrated that switching in the a/␣ strain was repressed by the a1-␣2 complex, the same complex that repressed mating (31). Their results suggested that in order to switch, natural strains, which are predominantly a/␣ (26,30,48), first had to undergo homozygosis to a/a or ␣/␣. Lockhart et al. (30) generalized this observation by demonstrating that while natural a/␣ strains did not undergo white-opaque switching, spontaneously generated MTL-homozygous offspring and natural MTL-homozygous strains did switch. Miller and Johnson (31) further demonstrated that in order to mate, the a and ␣ strains they derived by deleting MTL␣2 and MTLa1, respectively, first had to switch from white to opaque. Lockhart et al. (29) generalized this observation by demonstrating that only natural a/a and ␣/␣ strains that expressed the opaque phenotype could mate. The white-opaque transition, therefore, was an essential and unique step in the C. albicans mating process (3,42,43).In spite of the fundamental role white-opaque switching plays in mating, very little is known about the molecular mechanisms that re...

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Different patterns of gene silencing in position-effect variegation

Cited by 21 publications

References 31 publications

Clinical, Cytogenetic and Molecular Study in a Case of r(3) with 3p Deletion and Review of the Literature

Clinical, Cytogenetic and Molecular Study in a Case of r(3) with 3p Deletion and Review of the Literature

FISH‐mapping of telomeric 14q32 deletions: Search for the cause of seizures

TOS9 Regulates White-Opaque Switching in Candida albicans

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