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We hypothesized that the maternal Dlk1 allele may acquire methylation at a later stage of development or that the hypermethylation we observed on the maternal allele was an adult tissue-specific pattern.
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It was found that instead of loss in methylation, subtelomeres may acquire dense methylation in some specific cell lines such as in SK-LU-1, towards telomere lengthening [ 21].
Thus, two identical and closely located ICR2 sequences may acquire different methylation imprints, indicating that features, in addition to the ICR2 sequence itself, are necessary for imprinting establishment.
Our results revealed a higher frequency of methylation in cell lines (83 100%) but lower in primary tumours (29 34%), indicating that some cell lines may have acquired methylation during their establishment or maintenance process.
It thus seems that CTS1 was more prone to acquire methylation than CTS6.
High CpG density promoters, and in particular those mapping to developmental genes, acquire methylation, whereas CpGs located outside these regions tend to lose methylation with age.
These CpG islands are protected from de novo methylation in normal tissues, but often acquire methylation in cancer cells that leads to gene silencing.
It has also been suggested that some tumours may acquire a CpG island methylator phenotype, that is, concurrent methylation of genes occurring in a nonrandom manner (Toyota et al, 1999).
It may be speculated that besides HPRT and CDX1, a number of other CpG island-containing loci in tumour cells exposed to cytostatic therapy stress may acquire a concordant low-level methylation.
Down-regulation of BRCA1 mRNA and protein expression may be mediated by acquired methylation of the BRCA1 promotor or upstream pathway regulation malfunction [ 59].
In this case, either allele could be methylated, or there may be a preference for acquiring methylation on one parental allele due to other epigenetic marks differentiating the two parental chromosomes.
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