Differential expression of the eukaryotic genome through cell differentiation or response to environmental changes requires specific modulation of its nuclear organization. These processes enable regulated genes to prevail against regulatory constraints of chromatin structure in which DNA is wrapped around core nucleosomes consisting of octamers of histones H2A. H2B, H3 and H4. Overcoming the structural restriction of chromatin upon gene expression is achieved in part through the modulation of particular marks that define active or inactive chromatin domains.
DNA methyl transferases establish and maintain the pattern of genomic DNA methylation on cytosines of CpG dinucleotides. This cpigenetic mark is linked to gene repression: hypomethylated DNA is associated with active genes, whereas hypermethylated genes are silent.
Although gene expression correlates with CpG demethy-lation, processes that either remove the 5-methyl group or that exchange methylated cytosines with cytosines are yet to be elucidated. .
Processes that regulate gene transcription are directly under the influence of the genome organization. The epigenome contains additional information that is not brought by DNA sequence, and generates spatial and functional constraints that complement genetic instructions.
Metivier et al in Nature 6th march 2008 present evidence of a dynamic role for DNA methylation in gene regulation in human cells. Periodic, strand-specific methylation/demethylation occurs during transcriptional cycling of the pS2/TFFl gene promoter on activation by oestrogens.
DNA methyltransferases exhibit dual actions during these cycles, being involved in CpG methylation and active demethylation of 5mCpGs through deamination. Inhibition of this process precludes demethylation of the pS2 gene promoter and its subsequent transcriptional activation. Cyclical changes in the methylation status of promoter CpGs may thus represent a critical event in transcriptional achievement.
The interesting point here for nutritionists is that if oestrogen act in this manner then soy products which have an mild oestrogenic activity might also
Metivier et al 2008 Cyclical DNA methylation of a transcriptionally active promoter Nature vol 452, pp 45-50
- Martin Eastwood