Monoallelic Gene Expression in Mice: Who? When? How? Why?
- The Jackson Laboratory, Bar Harbor, Maine 04609, USA
This extract was created in the absence of an abstract.
In this issue, Sano et al (2001) describe a cluster of three genes in the mouse t complex that exhibit random monoallelic expression, representing a new example of somatic mosaicism. These findings are fascinating from several perspectives, raising questions that make for entertaining speculation by casual and dedicated observers of the epigenetics field. What is the biological reason for monoallelic expression? What is the mechanism? Is it just stochastic or is it a critical mode of transcriptional regulation? Do monoallelically-expressed genes occur primarily in clusters?
Link to Methylation
One key aspect of Sano et al.'s findings was the correlation between methylation status and the expression (or non-expression) of the alleles. In the cell types investigated by Southern blot analysis with the enzymes HpaII and MspI, approximately half the genomic DNA could be cleaved at certain HpaII sites, indicating that half the sites were methylated. However, it was not determined directly if the non-expressed allele was also the methylated allele, or vice versa. Nevertheless, this observation has potential significance with respect to mechanism. If the methylation state is what dictates which allele is active, then this would eliminate the possibility that monoallelic expression is a consequence of limiting amounts of cognate transcription factors. The other important issue to consider is the clustering of the three monallelically-expressed genes. Is this a coincidence, or do alleles on the same chromosome undergo silencing or activation in a coordinated way? If the latter is true, a chromatin-driven type of mechanism would again be implicated, as opposed to one invoking limiting quantities of transcription factors. This question of clustering could be tested if the expressed allele of all three of the genes discovered by Sano and colleagues were determined in individual cells.
How Does it Work?
To further build on the speculation that the selection of alleles for expression is …
