G9a co-suppresses LINE1 elements in spermatogonia.

Area of Science:

• Epigenetics
• Reproductive Biology
• Genomics

Background:

• Retrotransposon repression is vital for genome integrity and germ cell development.
• The piRNA pathway and DNA methylation are key for silencing LINE1 (L1) and IAP retrotransposons in embryonic germ cells.
• Histone H3 lysine 9 dimethylation (H3K9me2) is proposed to co-repress L1 elements in mitotic spermatogonia.

Purpose of the Study:

• To investigate the role of G9a-mediated H3K9me2 in L1 retrotransposon silencing in spermatogonia.
• To understand the distinct requirements for L1 and IAP retrotransposon silencing in adult spermatogenesis.
• To assess the impact of retrotransposon activation on spermatogonial populations and testicular homeostasis.

Main Methods:

• Investigated the function of G9a in L1 silencing in spermatogonia.
• Assessed the sufficiency of H3K9me2 for IAP silencing.
• Analyzed the consequences of losing multiple retrotransposon repressive mechanisms on germ cell populations.

Main Results:

• G9a is essential and sufficient for L1 silencing in spermatogonia when piRNA and DNA methylation pathways are absent.
• H3K9me2 alone is insufficient for maintaining IAP silencing in spermatogonia.
• Loss of all three repressive mechanisms severely impacts spermatogonial populations, including stem cells, leading to germ cell loss.

Conclusions:

• G9a-mediated H3K9me2 is a novel and critical mechanism for L1 repression in the germ line.
• L1 and IAP retrotransposons exhibit different silencing maintenance requirements in adult spermatogenesis.
• Retrotransposon repression in spermatogonia is crucial for maintaining germ cell population survival and testicular homeostasis.