For autosomes, major satellite DNA forms chromocenters at pericentromeric heterochromatin where Histone 3 is phosphorylated (PH3) and chromosome condensation is initiated. However, the mouse Y chromosome lacks major satellite DNA, so how the mouse Y initiates chromosome condensation is not known.
Immuno-FISH showed the Sertoli cell nucleus of fetal mouse testes contains a single PML nuclear body enriched for GATA4 (GATA4-PML-NB). Also in the GATA4-PML-NB is Y chromosome region comprising GATA4 DNA binding motifs, and heterochromatin protein 1 alpha (HP1a), PH3 and ATRX chromatin remodeller.
ATR-X syndrome is a condition that affects boys characterised by intellectual disability, alpha thalassemia, and XY male-to-female sex reversal1. We generated mice with Atrx inactivated in Sertoli cells (Atrx KO) to mimic the gonadal phenotype of ATR-X syndrome. These mice show testicular dysgenesis due to cell cycle arrest at G2 and apoptosis of fetal Sertoli cells2.
In Atrx KO testes, the GATA4-PML-NBs are up to 3-fold larger (~3mm), lack HP1a and PH3 expression, and show double-strand DNA breaks (gH2AX), indicative of a failure in chromosome condensation.
In summary Y chromosome condensation in mouse Sertoli cells requires ATRX at a single unique PML-NB, rich in GATA4. The GATA4-PML-NB marks a chromatin region on the mouse Y chromosome that might function as a chromocenter. Analogous to major satellite DNA on autosome where chromosome condensation initiates, GATA-rich sequences on Y chromosome might the nucleate Y chromosome condensation.