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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

Methylation staining on DFT chromosomes. a DAPI image, b methylation staining and c merged image showing methylation staining on strain 4 chromosomes. d karyotype of chromosomes depicted in images a-c. e karyotype of a tetraploid strain 1 tumour
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Fig6: Methylation staining on DFT chromosomes. a DAPI image, b methylation staining and c merged image showing methylation staining on strain 4 chromosomes. d karyotype of chromosomes depicted in images a-c. e karyotype of a tetraploid strain 1 tumour

Mentions: Similar to chromosomes from devil fibroblast, all DFTD chromosomes, including the rearranged marker chromosomes, displayed strong telomeric region methylation, and little interstitial methylation (Fig. 6a-d). It is particularly interesting that the marker chromosomes, for which the original telomeres would have been lost during rearrangement, have reinstated methylation of telomeric regions. Methylation of these regions may therefore be important for telomere length maintenance and tumour persistence.Fig. 6


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

Ingles ED, Deakin JE - Mol Cytogenet (2015)

Methylation staining on DFT chromosomes. a DAPI image, b methylation staining and c merged image showing methylation staining on strain 4 chromosomes. d karyotype of chromosomes depicted in images a-c. e karyotype of a tetraploid strain 1 tumour
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig6: Methylation staining on DFT chromosomes. a DAPI image, b methylation staining and c merged image showing methylation staining on strain 4 chromosomes. d karyotype of chromosomes depicted in images a-c. e karyotype of a tetraploid strain 1 tumour
Mentions: Similar to chromosomes from devil fibroblast, all DFTD chromosomes, including the rearranged marker chromosomes, displayed strong telomeric region methylation, and little interstitial methylation (Fig. 6a-d). It is particularly interesting that the marker chromosomes, for which the original telomeres would have been lost during rearrangement, have reinstated methylation of telomeric regions. Methylation of these regions may therefore be important for telomere length maintenance and tumour persistence.Fig. 6

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