Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta

Abstract

Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility 1 . Here we show that Cnot7 -/-males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor 2 , is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of Cnot7 -/-mice. Transplantation of spermatogonial stem cells from male Cnot7 -/-mice to seminiferous tubules of Kit mutant mice (Kit W/W-v ) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7 -/-condition. The testicular phenotypes of Cnot7 -/-mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb) 3 . We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.

Arabidopsis Deadenylases AtCAF1a and AtCAF1b Play Overlapping and Distinct Roles in Mediating Environmental Stress Responses

“…In eukaryotes, such as yeast, fly, mouse, and human, CAF1 homologs have been identified and shown to be important for deadenylation. Furthermore, in these species there are only one or two CAF1 genes (Albert et al, 2000;Daugeron et al, 2001;Nakamura et al, 2004;Temme et al, 2004;Yamashita et al, 2005). In contrast, our results demonstrate that there has been an expansion of the CAF1 gene family in angiosperms ( Fig.…”

“…In other eukaryotes such as yeast, fly, mouse, and human there are only one or two CAF1 genes ( Fig. 2; Albert et al, 2000;Daugeron et al, 2001;Nakamura et al, 2004;Temme et al, 2004;Yamashita et al, 2005).…”

“…Additionally, CAF1 is required for normal growth of trypanosomes (Schwede et al, 2008). Finally, mice lacking CAF1 are sterile (Nakamura et al, 2004).…”

Interaction of CCR4–NOT with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis

“…In line with our findings, DNA binding by RXRα was shown to be enhanced by its interaction with the CNOT7 subunit of the CCR4-NOT complex (Nakamura et al 2004). CNOT7 interacts with a specific domain of RXRα in Sertoli cells, and DNA binding and transcriptional activation by RXRα were found to be impaired in CNOT7-deficient testis extracts and CNOT7-deficient mouse embryonic fibroblasts, respectively (Nakamura et al 2004). In embryonic stem cells, ChIP-seq analysis detecting CNOT3 occupancy revealed an enriched consensus sequence, 5 ′ -CGGCNGCG, and suggested the possibility of sequence-specific binding by CNOT3 (Hu et al 2009).…”

“…The sequences of "H240A-sensititive" and "H240A-insensitive" EBF1-binding sites are similar, suggesting that the chromatin context may influence the contribution of the CCR4-NOT complex to EBF1 occupancy in vivo. In line with our findings, DNA binding by RXRα was shown to be enhanced by its interaction with the CNOT7 subunit of the CCR4-NOT complex (Nakamura et al 2004). CNOT7 interacts with a specific domain of RXRα in Sertoli cells, and DNA binding and transcriptional activation by RXRα were found to be impaired in CNOT7-deficient testis extracts and CNOT7-deficient mouse embryonic fibroblasts, respectively (Nakamura et al 2004).…”