The oocyte‐specific transcription factor, Nobox, regulates the expression of Pad6, a peptidylarginine deiminase in the oocyte

Abstract

a b s t r a c tNobox is an oocyte-specific transcriptional regulator. Nobox deficiency disrupts early folliculogenesis and the expression of oocyte-specific genes in mice. In the present study, we found that peptidylarginine deiminase 6 (Pad6) was downregulated in Nobox-null ovaries. Pad6 is preferentially expressed in oocytes and its transcript is detectable at embryonic day 16.5. In addition, we identified one Nobox DNA-binding element (NBE) within the mouse Pad6 promoter. The NBE includes a core sequence TAATTA. Sequence-specific binding of Nobox to the TAATTA motif was confirmed. Nobox overexpression augmented transcriptional activity of a luciferase reporter driven by mouse Pad6. Our findings indicate that Nobox is a critical regulator that orchestrates oocyte-specific genes such as Pad6 during folliculogenesis.

HSP90 Antibodies: A Detrimental Factor Responsible for Ovarian Dysfunction

“…Nobox is an oocyte specific transcriptional regulator and is expressed by germ cell cysts, primordial, and growing follicles . Deficiency of this molecule has been shown to disrupt early folliculogenesis and the expression of several oocyte specific genes in mice . Gap junctions between cumulus and oocyte predominantly contain Gja1 protein.…”

The NOBOX protein becomes undetectable in developmentally competent antral and ovulated oocytes

“…Whilst the expression of the Nobox gene has already been described in a number of earlier studies in both mouse (Suzumori et al, 2002;Rajkovic et al, 2004;Choi and Rajkovic, 2006;Choi et al, 2010) and human (Huntriss et al, 2006;Qin et al, 2007), the presence of the NOBOX protein throughout oocyte growth in the adult ovary has never been shown before. The acquisition of this knowledge is central to the understanding of the regulatory role, attributed to the NOBOX protein, upstream of a number of genes crucial to oocyte growth e.g., Oct4, Gdf9, Bmp15, Fgf8, H1oo, Mos, Rfpl4, Zar1 and Dnmt1o (Rajkovic et al, 2004;Choi and Rajkovic, 2006).…”

Aetiological coding sequence variants in non-syndromic premature ovarian failure: From genetic linkage analysis to next generation sequencing

“…Gdf9, Bmp15,Pou5f1,Zar1,Oog1,Pad6,Oosp1,Oct4) are directly or indirectly regulated by NOBOX because KO mice have shown differential expression patterns compared to wild type (WT) animals (Rajkovic et al, 2004). Direct binding to promoter regions has been demonstrated for Gdf9, Pou5f1 and Pad6 (Choi et al, 2010;Choi and Rajkovic, 2006). Very recently, it has been shown that NOBOX and FOXL2 can form a complex to regulate specific target genes in granulosa cells (Bouilly et al, 2014).…”