Search PubMedSearch

Biomedical subjects

J R Vermeesch

Publications and source records attributed to J R Vermeesch.

6 recordsLinked to original sources

Differences in the distribution and nature of the interstitial telomeric (TTAGGG)n sequences in the chromosomes of the Giraffidae, okapai (Okapia johnstoni), and giraffe (Giraffa camelopardalis): evidence for ancestral telomeres at the okapi polymorphic rob(5;26) fusion site.

Intrachromosomal telomeric sequences (TTAGGG)n were analyzed in the two members of the family Giraffidae, the giraffe and the okapi. The giraffe has a diploid chromosome number of 2n = 30, whereas the okapi chromosome number varies from 2n = 46 to 2n = 45 and 2n = 44 due to a "recent" Robertsonian fusion event. The interstitial telomeres that we detected in these species are of two types: (1) In the okapi, a long interstitial telomeric element is present at the fusion site of the rob(4;26). The nature of this interstitial telomeric element suggests that it is a remnant of the telomeres of the ancestral chromosomes that participated in the fusion event. (2) In the giraffe, short stretches or degenerate telomeric sequences which are part of the satellite DNA are present at intrachromosomal sites. The results of this study provide insights into the origin of interstitial telomeric sequences in the Giraffidae.

Animals

The IL-9 receptor gene (IL9R): genomic structure, chromosomal localization in the pseudoautosomal region of the long arm of the sex chromosomes, and identification of IL9R pseudogenes at 9qter, 10pter, 16pter, and 18pter.

Cosmids containing the human IL-9 receptor (R) gene (IL9R) have been isolated from a genomic library using the IL9R cDNA as a probe. We have shown that the human IL9R cDNA as a probe. We have shown that hte human IL9R gene is composed of 11 exons and 10 introns, stretching over approximately 17 kb, and is located within the pseudoautosomal region of the Xq and Yq chromosome, in the vicinity of the telomere. Analysis f the 5' flanking region revealed multiple transcription initiation sites as well as potential binding motifs for AP1, AP2, AP3, Sp1, and NF-kB, although this region lacks a TATA box. Using the human IL9R cosmid as a probe to perform fluorescence in situ hybridization, additional signals were identified in the subtelomeric regions of chromosomes 9q, 10p, 16p, and 18p. IL9R homologs located on chromosomes 16 and 10 were completely sequenced. Although they are similar to the IL9R gene (approximately 90% identity), none of these copies encodes a functional receptor: none of them contains sequences homologous to the 5' flanking region or exon 1 of the IL9R gene, and the remaining ORFs have been inactivated by various point mutations and deletions. Taken together, our results indicate that the IL9R gene is located at Xq28 and Yq12, in the long arm pseudoautosomal region, and that four IL9R pseudogenes are located on 9q34, 10p15, 16p13.3, and 18p11.3, probably dispersed as the result of translocations during evolution.

Alternative Splicing

Telomeric DNA sequence and structure following de novo telomere synthesis in Euplotes crassus.

To learn more about the mechanism of de novo telomere synthesis, we have characterized the sequence and structure of newly synthesized telomeres from Euplotes crassus. E. crassus is a particularly useful organism for studying telomere synthesis because millions of telomeres are made in each cell at a well-defined time during the sexual stage of the life cycle. These newly synthesized telomeres are approximately 50 bp longer than mature macronuclear telomeres. We have investigated the structure of the newly synthesized telomeres and have found that they are much more heterogeneous in length than mature telomeres. Most of the heterogeneity is present on the G-rich strand, indicating that the length of this strand is rather loosely controlled. In contrast, the length of the C-rich strand is much less variable, suggesting that synthesis of this strand is the more precisely regulated step in telomere addition. The G-rich strand exhibits variability both in the total number of G4T4 repeats and in the identity of the terminal nucleotide. In most cases, the G-rich strnd extends beyond the C-rich strand to leave a 3' overhang. While the size of this overhang is variable, the median length is 10 nucleotides. This research provides the first detailed picture of a newly synthesized telomere and has allowed us to formulate a model to describe the various steps involved in de novo telomere synthesis.

Animals

Telomere processing in Euplotes.

In Euplotes crassus millions of telomeres are synthesized during the sexual phase of the life cycle. Since these newly synthesized telomeres are longer than normal macronuclear telomeres, they must be trimmed to the mature size. We have examined the timing and mechanism of this trimming step. We have shown that a sudden decrease in telomere length takes place at a specific time during macronuclear development. The decrease in telomere length is not caused by incomplete replication of the most terminal DNA sequences; rather it is the result of an active processing event that occurs independently of DNA replication. The developmentally regulated telomere shortening that takes place in Euplotes is reminiscent of the sudden reductions in telomere length which have been observed in other eukaryotes.

Animals

Accumulation of telomerase RNA and telomere protein transcripts during telomere synthesis in Euplotes.

In the ciliate Euplotes crassus a complex series of developmental events lead to formation of a new macronucleus. Millions of telomeres are synthesized during this process. We have shown that transcript levels are tightly regulated throughout Euplotes conjugation and macronuclear development. Thus, expression of gene products needed for macronuclear development and telomere synthesis appears to be controlled at the level of RNA abundance. To learn more about the role played by telomerase and the Euplotes telomere protein during telomere synthesis, we have correlated changes in the abundance of telomerase RNA and telomere protein mRNA transcript with specific developmental events. Telomerase RNA levels increase steadily during the early stages of macronuclear development and reach a peak just after telomere addition. The telomere protein transcript rises and falls twice during conjugation and then rises again at the time of telomere addition. The increases in transcript levels during conjugation parallel micronuclear division suggesting that the telomere protein is synthesized at this time and hence may have a micronuclear function.

Actins