Tissue specific expression of avian vitellogenin gene is correlated with DNA hypomethylation and in vivo specific protein-DNA interactions

Abstract

The avian vitellogenin gene is expressed only in the liver of egg-laying hens. It can, however, be activated in immature chicks or roosters by oestradiol. Parallel to the onset of transcription, there is a demethylation of specific mCpGs in the promoter region and in the oestrogen response element (ERE). The methylation pattern in the promoter region is hormone and expression specific, whereas in the ERE it is only hormone and not organ specific. The demethylation occurring in the promoter region is correlated with the appearance of DNase I hypersensitivity sites and changes in the specific protein-DNA interactions. In vivo genomic footprinting of the ERE with varying concentrations of dimethylsulphate revealed, upon gene activation, only minor changes in the protein-DNA interaction. We present evidence that there is another protein that binds with high affinity to the ERE, besides the oestrogen receptor.

Promoter demethylation in MMTV/N‐rasN transgenic mice required for transgene expression and tumorigenesis

“…The active process may be carried out by an excision-repair mechanism, as demonstrated in chicken embryos [26]. The existence of a demethylase is questioned by the irreversibility of cytosine methylation in carbon 5 at physiological pH [27]. Passive demethylation depends on inhibition of maintenance methylation, which occurs soon after replication and is, therefore, dependent on cell division.…”

Mechanisms for the Control of Gene Activity During Development

“…The technique of genomic sequencing was introduced in detailed studies of vitellogenin synthesis in the hen oviduct (Saluz et Jost et al, 1990). The technique of genomic sequencing was introduced in detailed studies of vitellogenin synthesis in the hen oviduct (Saluz et Jost et al, 1990).…”

“…There is, however, evidence that the active demethylation of cytosine at specific sites in DNA occurs in association with the activation of genes. The technique of genomic sequencing was introduced in detailed studies of vitellogenin synthesis in the hen oviduct (Saluz et al, 1986(Saluz et al, , 1988Jost et al, 1990). This makes it possible to study all the methylated cytosines in a given region, not only those in specific restriction enzyme sequences.…”

Structure, function and regulation of mammalian DNA methyltransferase

“…Fourth, it is possible that de novo methylation is indiscriminate and that tissuespecific methylation patterns are established by sequence-specific demethylation. Sequence-specific demethylation, presumably through a mechanism related to excision repair, has been documented in the case of the chicken vitellogenin gene (Jost et al, 1990) and could be widespread. It is sobering to recognize that at the present time it is not known whether tissue-specific methylation patterns are established by sequencespecific de novo methylation, by indiscriminate de novo methylation and sequence-specific demethylation, or by some combination of the two.…”

“…At such times the de novo activity of DNA MTase might be stimulated by proteolytic cleavage between the N-and C-terminal domains or interaction with a factor which counteracts the inhibitory effects of the N-terminal domain. The masking model cannot be looked on with much favor, as it is precisely the unmethylated CpG sites which are accessible to diffusible factors in nuclei (Antequera et al, 1989), and genomic sequencing has not shown a bias in the sequences Banking methylated and unmethylated CpG sites (Jost et al, 1990). Sequencespecific masking proteins would be expected to leave some evidence of a consensus sequence around unmethylated CpG sites.…”