TET1-JMJD3-H3K27me3 targets and regulates Pramel3 to affect spermatogonia self-renewal and proliferation and differentiation
Histone modification and DNA methylation among epigenetic modifications play a coordinated role in the regulation of spermatogonia. Tet methylcytosine dioxygenase 1 (TET1) can either act as a DNA demethylase, converting 5-methylcytosine to 5-hydroxymethylcytosine or regulate gene expression by forming a complex with other proteins. Increased levels of H3K27me3 will result in transcriptional repression and reduced or silenced protein expression. However, the mechanism by which TET1 mediates the regulation of H3K27me3 in spermatogonia and the target genes that act is not clear. The results of this study showed that the expression of self-renewal-related gene GFRA1 and proliferation-related gene PCNA were up-regulated after JMJD3 overexpression. Moreover, it was demonstrated that TET1 and JMJD3 can interact with H3K27me3 by forming a protein complex, and the CHIP-Seq sequencing results analyzed that TET1 targets and regulates the Pramel3 gene when interacting with H3K27me3, and TET1 overexpression promotes the up-regulation of Pramel3 expression. Our study identified a novel link between TET1 and H3K27me3 and established a TET1-JMJD3-H3K27me3-Pramel3 regulatory axis to regulate spermatogonia self-renewal, proliferation and differentiation. It provides a new idea to further investigate the mechanism of spermatogenesis and spermatogenic disorders from the epigenetic level. Overall design: Chromatin immunoprecipitation DNA sequencing (CHIP-seq) of histone modified H3K27me3 in GC-1 cells