Meiotic gatekeeper STRA8 regulates cell cycle by interacting with SETD8 during spermatogenesis

Abstract

STRA8 (Stimulated By Retinoic Acid Gene 8) is a retinoic acid (RA) induced gene that plays vital roles in spermatogonial proliferation, differentiation and meiosis. The SETD8 and STRA8 protein interaction was discovered using the yeast two‐hybrid technique using a mouse spermatogonial stem cell (SSC) cDNA library. The interaction of these two proteins was confirmed using co‐immunoprecipitation and identification of key domains governing the protein: protein complex. STRA8 and SETD8 showed a mutual transcriptional regulation pattern that provided evidence that SETD8 negatively regulated transcriptional activity of the STRA8 promoter. The SETD8 protein directly bound to the proximal promoter of the STRA8 gene. STRA8 increased the transcriptional activity of SETD8 promoter in a dose‐dependent manner. For the first time, we have discovered that STRA8 and SETD8 display a cell cycle‐dependent expression pattern in germline cells. Expression levels of SETD8 and H4K20me1 in S phase of STRA8 overexpression GC1 cells were different from that previously observed in tumour cell lines. In wild‐type mice testis, SETD8, H4K20me1 and PCNA co‐localized with STRA8 in spermatogonia. Further, our studies quantitated abnormal expression levels of cell cycle and ubiquitination‐related factors in STRA8 dynamic models. STRA8 and SETD8 may regulate spermatogenesis via Cdl4‐Clu4A‐Ddb1 ubiquitinated degradation axis in a PCNA‐dependent manner.

Transcriptome profiling of histone writers/erasers enzymes across spermatogenesis, mature sperm and pre-cleavage embryo: Implications in paternal epigenome transitions and inheritance mechanisms

“…At this stage there is de novo formation of bivalent domains by H3K27me deposition at developmental genes (Maezawa et al, 2018). Her, we detected peak expression of the H4K20me1 writer Setd8 , which was found to physically interact with STRA8 and to mutually control each other transcription (Niu et al, 2020). Moreover, SETD8, H4K20me1 and PCNA co-localize with STRA8, indicating a role for SETD8 in the cell cycle transition from mitosis to meiosis (Niu et al, 2020).…”

“…Her, we detected peak expression of the H4K20me1 writer Setd8 , which was found to physically interact with STRA8 and to mutually control each other transcription (Niu et al, 2020). Moreover, SETD8, H4K20me1 and PCNA co-localize with STRA8, indicating a role for SETD8 in the cell cycle transition from mitosis to meiosis (Niu et al, 2020). We also found peak expression of H3K36me Kdm2a and H3K9/K36me Kdm4a/b/c erasers.…”

Dimethyloxaloylglycine promotes spermatogenesis activity of spermatogonial stem cells in Bama minipigs

“…These 3 genes were respectively expressed in early, intermediate, and late stages of spermatogenesis. Stra8 is a meiosis gatekeeper [ 20 ]. Tnp1 is a post-meiotic gene and participates in nuclear transition [ 21 ].…”

Overexpression of DAZL, STRA8, and BOULE Genes and Treatment With BMP4 or Retinoic Acid Modulate the Expression of MSC Overexpressing Germ Cell Genes

“…Previously, it has been reported that a combined or individual overexpression of DAZL, STRA8, or BOULE in goat BM-MSCs resulted in the upregulation of OCT4 ( 22 , 23 ). Even though the molecular mechanism of STRA8 remains unclear, recently, it has been reported that STRA8 may regulate spermatogenesis via the Cdl4-Clu4A-Ddb1 ubiquitinated degradation axis in a proliferating cell nuclear antigen (PCNA)-dependent manner ( 38 ). On the other hand, DAZL has been associated to several molecules including the polyribosomes and poly(A)-binding proteins (PABPs), which suggests its participation in several aspects of protein synthesis including mRNA stability, transportation, localization, or translation ( 39 ).…”