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Publication : Znhit1 controls meiotic initiation in male germ cells by coordinating with Stra8 to activate meiotic gene expression.

First Author  Sun S Year  2022
Journal  Dev Cell Volume  57
Issue  7 Pages  901-913.e4
PubMed ID  35413238 Mgi Jnum  J:348727
Mgi Id  MGI:7643656 Doi  10.1016/j.devcel.2022.03.006
Citation  Sun S, et al. (2022) Znhit1 controls meiotic initiation in male germ cells by coordinating with Stra8 to activate meiotic gene expression. Dev Cell 57(7):901-913.e4
abstractText  The switch from mitosis to meiosis ensures the successive formation of gametes. However, it remains unclear how meiotic initiation occurs within the context of chromatin. Recent studies have shown that zinc finger HIT-type containing 1 (Znhit1), a subunit of the SRCAP chromatin remodeling complex, plays essential roles in modulating the chromatin structure. Herein, we report that the germline-conditional deletion of Znhit1 in male mice specifically blocks meiotic initiation. We show that Znhit1 is required for meiotic prophase events, including synapsis, DNA double-strand break formation, and meiotic DNA replication. Mechanistically, Znhit1 controls the histone variant H2A.Z deposition, which facilitates the expression of meiotic genes, such as Meiosin, but not the expression of Stra8. Interestingly, Znhit1 deficiency disrupts the transcription bubbles of meiotic genes. Thus, our findings identify the essential role of Znhit1-dependent H2A.Z deposition in allowing activation of meiotic gene expression, thereby controlling the initiation of meiosis.
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