Introduction

The Transcription Complex

Basic Cis-acting Sequences

Enhancers and Silencers

Methylation

Trans-acting Factors

Signaling Control of Transcription

Hormonal Control of Gene Expression

Signal Transduction Pathways

Study Questions

Control of Gene Expression in Eukaryotes WWW Links

Genetic Topics

Methylation

One common feature among eukaryotic organisms is the presence of methyl (-CH3) groups attached to DNA. Although they are not defined sequences, it has been suggested by correlation that they are involved in controlling gene expression. Specifically, the methyl group appears to be preferentially associated with cytosine bases, and the modified base is called 5'-methylcytosine (5'-mC). The percentage of 5'-mC varies between plants and animals.

Organism % 5'-mC
Animals

2-7%

Plants

>25%

Physically, the 5'-mC group occupies an open space inside the double-stranded DNA molecule. This observation has suggested that this group could act as a specific signal to other molecules that act to regulate gene expression.

Several observations have been made that support this hypothesis. In general, it has been demonstrated experimentally that there is a correlation between the levels of methylation and gene expression.

Low 5'-mC-------------> high levels of gene expression

High 5'-mC ------------> low levels of gene expression

Other observations have also been made. First, the methylation pattern is heritable from generation to generation. This obviously would be required if methylation is important for regulation because the pattern would be correlated with the specific features of that species. Next, the methylation pattern appears to be tissue specific. This would be expected if only a subset of all the genes in the genome are to be expressed in a single tissue type. It is thought that this is accomplished by the action of tissue specific demethylases.

5'-mC does not appear at random cytosine residues, but is mostly sequence specific. The methylation of cytosine primarily occurs at the sequence 5'-CpG-3'. The vast majority of methylation appears to be related to this sequence. An associated observation is that CpG islands exist that are often associated with genes. In mammals, about 30,000 CpG islands about 1-2 kb in size have been detected. Therefore, demethylation would occur in or near one of these islands, and those genes associated with that demethylated island would be expressed.

Copyright © 1997. Phillip McClean