A closer look revealed that MOF binds differently to chromosomes from males and females. On autosomes, chromosomes that are not involved in determining sex, and the X chromosome in females, MOF binds mostly to the beginning of a gene where transcription starts. On the X chromosome in males, however, MOF binds also towards the end of the gene. Most likely MOF opens up the DNA towards the end of the genes and ensures that transcription is completed successfully.
One can imagine the transcriptional machinery moving along the DNA like a train on a railway track. When the tracks are blocked the train could derail, resulting in incomplete transcription, explains Juanma Vaquerizas of Luscombes lab, who contributed to the analysis of Akhtars data. It appears that MOF clears the tracks throughout the male X chromosome, while on a female X obstructions are more likely to occur.
More complete transcription results in more proteins produced from the single X chromosome in males than from either of the two X chromosomes in females, thereby balancing out their excess. MOF is the first enzyme in the MSL complex to behave differently according to whether the target gene is located on the sex chromosome versus other chromosomes in males.
MOF is conserved across species and also has a human homolog. Since the mechanism of dosage compensation is radically different in mammals, it will be very interesting to discover what functional role this enzyme might play in that context, says Bertone.
|Contact: Anna-Lynn Wegener|
European Molecular Biology Laboratory