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Global DNA Methylation patterns on marsupial and devil facial tumour chromosomes.

Ingles ED, Deakin JE - Mol Cytogenet (2015)

Bottom Line: In males, the X chromosome was hypermethylated as was one X in females.Similarly, telomeric regions on DFTD chromosomes and regions corresponding to material from one of the two X chromosomes were hypermethylated.No difference in global methylation in samples of the same strain taken in different years was observed.

View Article: PubMed Central - PubMed

Affiliation: Institute for Applied Ecology, University of Canberra, Canberra, ACT 2601 Australia.

ABSTRACT

Background: Despite DNA methylation being one of the most widely studied epigenetic modifications in eukaryotes, only a few studies have examined the global methylation status of marsupial chromosomes. The emergence of devil facial tumour disease (DFTD), a clonally transmissible cancer spreading through the Tasmanian devil population, makes it a particularly pertinent time to determine the methylation status of marsupial and devil facial tumour chromosomes. DNA methylation perturbations are known to play a role in genome instability in human tumours. One of the interesting features of the devil facial tumour is its remarkable karyotypic stability over time as only four strains with minor karyotypic differences having been reported. The cytogenetic monitoring of devil facial tumour (DFT) samples collected over an eight year period and detailed molecular cytogenetic analysis performed on the different DFT strains enables chromosome rearrangements to be correlated with methylation status as the tumour evolves.

Results: We used immunofluorescent staining with an antibody to 5-methylcytosine on metaphase chromosomes prepared from fibroblast cells of three distantly related marsupials, including the Tasmanian devil, as well as DFTD chromosomes prepared from samples collected from different years and representing different karyotypic strains. Staining of chromosomes from male and female marsupial cell lines indicate species-specific differences in global methylation patterns but with the most intense staining regions corresponding to telomeric and/or centromeric regions of autosomes. In males, the X chromosome was hypermethylated as was one X in females. Similarly, telomeric regions on DFTD chromosomes and regions corresponding to material from one of the two X chromosomes were hypermethylated. No difference in global methylation in samples of the same strain taken in different years was observed.

Conclusions: The methylation patterns on DFTD chromosomes suggests that the hypermethylated active X was shattered in the formation of the tumour chromosomes, with atypical areas of methylation on DFTD chromosomes corresponding to locations of X chromosome material from the shattered X. The incredibly stable broad methylation patterns observed between strains and over time may reflect the overall genomic stability of the devil facial tumour.

No MeSH data available.


Related in: MedlinePlus

Marsupial phylogeny showing relationship of the species used in this and previous studies. Female haploid chromosome complements are colour-coded to indicate the homology between species
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Fig1: Marsupial phylogeny showing relationship of the species used in this and previous studies. Female haploid chromosome complements are colour-coded to indicate the homology between species

Mentions: The Tasmanian devil (Sarcophilus harrisii) is an interesting species in which to study methylation patterns on chromosomes. Firstly, it has a 2n = 14 karyotype similar to the predicted ancestral marsupial karyotype [5] (Fig. 1). Secondly, devil chromosomes display a remarkable telomere length dimorphism where one homologue of each chromosome has short telomeres while the other has long, with this dimorphism proposed to be due to a parent-of-origin effect and possibly epigenetically regulated [6]. Finally, and most importantly, the devil population has been decimated by a transmissible tumour known as devil facial tumour disease (DFTD). Some chromosomes in DFTD have undergone extensive rearrangement [7, 8], providing an opportunity to examine the effect of genome rearrangement on chromosome methylation. Changes in DNA methylation are common in tumours, with hypermethylation of promoter regions leading to the silencing of tumour suppressor genes and hypomethylation, particularly of repeat sequences, being associated with genome instability. The cytogenetic monitoring of DFT samples collected from 2005 to 2012 [9] and detailed molecular cytogenetic analysis performed on the different DFT strains [8], enables chromosome rearrangements to be correlated with changes in methylation status as the tumour evolves.Fig. 1


Global DNA Methylation patterns on marsupial and devil facial tumour chromosomes.

Ingles ED, Deakin JE - Mol Cytogenet (2015)

Marsupial phylogeny showing relationship of the species used in this and previous studies. Female haploid chromosome complements are colour-coded to indicate the homology between species
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4591559&req=5

Fig1: Marsupial phylogeny showing relationship of the species used in this and previous studies. Female haploid chromosome complements are colour-coded to indicate the homology between species
Mentions: The Tasmanian devil (Sarcophilus harrisii) is an interesting species in which to study methylation patterns on chromosomes. Firstly, it has a 2n = 14 karyotype similar to the predicted ancestral marsupial karyotype [5] (Fig. 1). Secondly, devil chromosomes display a remarkable telomere length dimorphism where one homologue of each chromosome has short telomeres while the other has long, with this dimorphism proposed to be due to a parent-of-origin effect and possibly epigenetically regulated [6]. Finally, and most importantly, the devil population has been decimated by a transmissible tumour known as devil facial tumour disease (DFTD). Some chromosomes in DFTD have undergone extensive rearrangement [7, 8], providing an opportunity to examine the effect of genome rearrangement on chromosome methylation. Changes in DNA methylation are common in tumours, with hypermethylation of promoter regions leading to the silencing of tumour suppressor genes and hypomethylation, particularly of repeat sequences, being associated with genome instability. The cytogenetic monitoring of DFT samples collected from 2005 to 2012 [9] and detailed molecular cytogenetic analysis performed on the different DFT strains [8], enables chromosome rearrangements to be correlated with changes in methylation status as the tumour evolves.Fig. 1

Bottom Line: In males, the X chromosome was hypermethylated as was one X in females.Similarly, telomeric regions on DFTD chromosomes and regions corresponding to material from one of the two X chromosomes were hypermethylated.No difference in global methylation in samples of the same strain taken in different years was observed.

View Article: PubMed Central - PubMed

Affiliation: Institute for Applied Ecology, University of Canberra, Canberra, ACT 2601 Australia.

ABSTRACT

Background: Despite DNA methylation being one of the most widely studied epigenetic modifications in eukaryotes, only a few studies have examined the global methylation status of marsupial chromosomes. The emergence of devil facial tumour disease (DFTD), a clonally transmissible cancer spreading through the Tasmanian devil population, makes it a particularly pertinent time to determine the methylation status of marsupial and devil facial tumour chromosomes. DNA methylation perturbations are known to play a role in genome instability in human tumours. One of the interesting features of the devil facial tumour is its remarkable karyotypic stability over time as only four strains with minor karyotypic differences having been reported. The cytogenetic monitoring of devil facial tumour (DFT) samples collected over an eight year period and detailed molecular cytogenetic analysis performed on the different DFT strains enables chromosome rearrangements to be correlated with methylation status as the tumour evolves.

Results: We used immunofluorescent staining with an antibody to 5-methylcytosine on metaphase chromosomes prepared from fibroblast cells of three distantly related marsupials, including the Tasmanian devil, as well as DFTD chromosomes prepared from samples collected from different years and representing different karyotypic strains. Staining of chromosomes from male and female marsupial cell lines indicate species-specific differences in global methylation patterns but with the most intense staining regions corresponding to telomeric and/or centromeric regions of autosomes. In males, the X chromosome was hypermethylated as was one X in females. Similarly, telomeric regions on DFTD chromosomes and regions corresponding to material from one of the two X chromosomes were hypermethylated. No difference in global methylation in samples of the same strain taken in different years was observed.

Conclusions: The methylation patterns on DFTD chromosomes suggests that the hypermethylated active X was shattered in the formation of the tumour chromosomes, with atypical areas of methylation on DFTD chromosomes corresponding to locations of X chromosome material from the shattered X. The incredibly stable broad methylation patterns observed between strains and over time may reflect the overall genomic stability of the devil facial tumour.

No MeSH data available.


Related in: MedlinePlus