Abstract:
:ESR1 is frequently silenced by CGI (CpG island) methylation, both in human colorectal tumours and, in an age-dependent manner, in healthy mucosa. It is not clear, however, whether methylation of individual cytosines occurs randomly within the epithelial genome, or preferentially within individual cells as an 'all-or-nothing' phenomenon. CGI methylation can be quantified in human DNA residues recovered from faecal samples. We used bisulphite genomic sequencing of human DNA from this source and from a colorectal cancer cell line (SW48) to show that the ESR1 CGI is methylated in an allele-specific manner. This provides support for the 'all or none' mechanism for methylation of this gene, and shows how age-dependent methylation of the ESR1 CGI leads rapidly to silencing of the gene within the cells, and hence the colonic crypt within which it occurs. Preliminary studies with a rodent model suggest the rate of age-dependent methylation of ESR1 is modifiable by dietary folate.
journal_name
Biochem Soc Transjournal_title
Biochemical Society transactionsauthors
Belshaw NJ,Elliott GO,Williams EA,Mathers JC,Buckley L,Bahari B,Johnson ITdoi
10.1042/BST0330709keywords:
subject
Has Abstractpub_date
2005-08-01 00:00:00pages
709-11issue
Pt 4eissn
0300-5127issn
1470-8752pii
BST0330709journal_volume
33pub_type
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