Study reveals mechanism that regulates genes on sex chromosomes

In the human population, males have one X and one Y chromosomes and females have two X chromosomes. As a result, somatic cells have unique mechanisms that maintain the same gene expression levels on the X chromosome between both genders.

Such a process is known as dosage compensation and has been widely investigated in the fruit fly Drosophila. A research team from the University of Tsukuba (UT) has now continued this study with Drosophila fly to demonstrate that dose compensation does not take place in the germ cells of male flies.

In a recent article, published in Scientific Reports journal, the UT researchers studied this phenomenon in fly primordial germ cells (PGCs), which are found in embryos and are the precursor cells to what eventually become eggs and sperm in adults. Previous studies performed on dosage compensation in this type of cell were contradictory.

Genetic analyses of somatic cells have demonstrated that the expression of X-linked genes in male fruit flies is up-regulated to reach corresponding levels to that of their female flies. The male-specific lethal (MSL) complex is a group of proteins that is responsible for performing this function.

These results made the UT team to find out if the same mechanism also takes place in the male germ cells. During embryonic development between female and male fruit flies, distinct molecular events take place in PGCs. Since the outcomes demonstrated in previous publications did not align, the team opted to handle their key question differently.

The MSL complex leaves a signature mark, called acetylation, on a specific amino acid of the histone H4 protein of the X chromosome. The acetyl group being added tells the cell to express the X-linked genes at a higher level, which results in dosage compensation.”

Satoru Kobayashi, Study Senior Author and Professor, University of Tsukuba

To deal with their questions, the team utilized a process known as transcriptome analysis to compare the expression levels of genes between male and female fruit fly PGCs. They also analyzed the protein histone H4 to find out if acetylation had taken place.

We found that X-linked gene expression in male PGCs was about half that of female PGCs. We also could not detect the acetylation signature of the MSL complex.”

Satoru Kobayashi, Study Senior Author and Professor, University of Tsukuba

Furthermore, the authors determined that the key components of the MSL complex are present only in very low quantities in the fly PGCs. Fascinatingly, transgenic flies were then produced that were designed to express higher levels of MSL complex proteins. In these flies, male PGCs showed higher expression of the X-linked genes, in addition to the acetylation signature.

According to the researchers, the study results have strong biological importance, potentially indicating that the lack of dosage compensation influences sex determination of Drosophila PGCs. This study also offers a new insight that will be important for additional analysis of germ cell maturation and embryo development.