The Modification of Tet1 in Male Germline Stem Cells and Interact with PCNA, HDAC1 to promote their Self-renewal and Proliferation

Abstract

Epigenetic modification plays key roles in spermatogenesis, especially DNA methylation dynamic is important in sustaining normal spermatogenesis. Ten-eleven translocation 1 (Tet1) is not only a key demethylase, which works in specific gene regions, but also crosstalks with partners to regulate epigenetic progress as protein complexes. Dairy goat is an important livestock in China, while the unstable culture system in vitro inhibits optimization of new dairy goat species. The study of epigenetic modification in male germline stem cells (mGSCs) is beneficial to the optimization of adult stem cell culture system in vitro, and the improvement of sperm quality and breeding of selected livestock. In our study, we not only analyzed the morphology, gene expression, DNA methylation and histone methylation dynamic in mouse Tet1 (mTet1) modified mGSCs, we also analyzed the stemness ability by in vivo transplantation and explored the functional mechanism of Tet1 in dairy goat mGSCs. The results showed mTet1 modified mGSCs had better self-renewal and proliferation ability than wild-type mGSCs, mTet1 could also up-regulate JMJD3 to decrease H3K27me3, which also showed to suppress the MEK-ERK pathway. Furthermore, Co-IP analysis demonstrated that TET1 interact with PCNA and HDAC1 by forming protein complexes to comprehensively regulate dairy goat mGSCs and spermatogenesis.

The chromatin remodeler LSH controls genome-wide cytosine hydroxymethylation

“…To explore the mechanisms of action of TETs, we identified TET protein partners via an unbiased proteomic approach using HaloTag technology as previously described (51). This approach identified several transcription factors and epigenetic proteins co-immunoprecipitating with TET proteins, including previously described binding partner OGT (10), PARP (52) and PCNA (53). We also identified the SNF2-helicase like LSH as a TET1 and TET3 binding partner with this method (data not shown).…”

Immunoprecipitation and Mass Spectrometry Define TET1 Interactome During Oligodendrocyte Differentiation

“…Except for DNA demethylation, TET1 also works in various ways and crosstalks with partners to regulate gene expression [21][22][23]. Then we searched for transcription factors (TFs) in TET1 interactome with TcoF-DB v2 database.…”

Noncoding RNAs: Potential players in the self‐renewal of mammalian spermatogonial stem cells

“…Another histone demethylase FBXL10 was shown to regulate the SSC proliferation via affecting cell cycle in mice (Ozawa, Fukuda, Sakamoto, Honda, & Yoshida, ). Interestingly, TET1, as an epigenetic regulator, not only modulates DNA methylation, also participates in histone modification to affect the ability of SSC self‐renewal (L. Zheng et al, ).…”

“…Interestingly, TET1, as an epigenetic regulator, not only modulates DNA methylation, also participates in histone modification to affect the ability of SSC self-renewal (L Zheng et al, 2016)…”