Msl3, a member of the chromatin-associated male-specific lethal MSL complex, is conserved from flies to humans. In Drosophila, it is crucial for the transcriptional upregulation of genes on the male X chromosome for dosage compensation [4].

In female Drosophila oogenesis, Msl3, acting independently of the rest of the MSL complex, promotes germline stem cell (GSC) differentiation. It does so by regulating the transcription of genes like RpS19b, which is required for the translation of Rbfox1, a meiotic cell cycle entry factor [1].

In mice, studies using a male germline-specific Stra8-iCre driver and a Msl3flox conditional knock-out (CKO) mouse line were conducted. Conditional loss-of-function of Msl3 in spermatogonia did not cause spermatogenesis defects or changes in meiosis-related gene expression. This indicates that in mice, Msl3 has a different expression pattern compared to Drosophila and primates, and loss-of-function mutations in its chromodomain alone do not impede meiotic entry [2,3].

In conclusion, Msl3 plays important roles in Drosophila GSC differentiation and dosage compensation. In mammals, despite conservation of the gene, its function in meiotic entry seems to differ from that in flies and primates as shown by the Msl3 CKO mouse model. In humans, de novo mutations in Msl3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation, highlighting its significance in human development [5].