Timing and Mechanism of Imprinting

Although the details of imprinting are still unknown, it is clear that imprinting must occur either during the formation of the gametes or immediately after fertilization, while the two chromosome sets are still distinct. The imprint must be reliably passed on to each new daughter chromosome during DNA replication.

The exact molecular mechanism of imprinting is also unknown, but it is thought to involve the modification of a gene's promoter. The promoter is the upstream region to which RNA polymerase binds to begin transcription. Imprinting prevents or restricts binding of RNA polymerase, thus preventing gene transcription.

One method by which a gene becomes imprinted is believed to be by the addition of methyl groups (-CH3) to cytosine nucleotides in the promoter region. The evidence for methylation is strong. Methylation is a common mechanism for gene silencing, because these bulky side groups interfere with the efficient binding of the various transcription factors required to attract the polymerase enzyme. Methylation patterns are known to be altered during gamete formation, and are reliably passed on during replication. Further evidence comes from the observation that altered methylation patterns in some imprinted genes are associated with the aberrant expression of the normally silent allele.

CH, promoter

IGF2 gene

Methylation of the promoter region is believed to be an important silencing region.

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