Department of Molecular Biosciences, The Wenner-Gren Institute
Ozata group publishes in RNA Journal
A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals
Tiangxiong Yu, Adriano Biasini, Katharine Cecchini, Martin Säflund, Haiwei Mou, Amena Arif, Atiyeh Eghbali, Dirk G. de Rooij, Zhiping Weng, Phillip D. Zamore and Deniz M. Özata
Abstract
In male mice, the transcription factor A-MYB initiates the transcription of pachytene piRNA genes during meiosis. Here, we report that A-MYB activates the transcription factor Tcfl5 produced in pachytene spermatocytes. Subsequently, A-MYB and TCFL5 reciprocally reinforce their own transcription to establish a positive feedback circuit that triggers pachytene piRNA production. TCFL5 regulates the expression of genes required for piRNA maturation and promotes transcription of evolutionarily young pachytene piRNA genes, whereas A-MYB activates the transcription of older pachytene piRNA genes. Intriguingly, pachytene piRNAs from TCFL5-dependent young loci initiate the production of piRNAs from A-MYB-dependent older loci, ensuring the self-propagation of pachytene piRNAs. A-MYB and TCFL5 act via a set of incoherent feedforward loops that drive regulation of gene expression by pachytene piRNAs during spermatogenesis. This regulatory architecture is conserved in rhesus macaque, suggesting that it was present in the last common ancestor of placental mammals.
As a new research group aiming to construct an international work environment with a mutual respect, our main objective is to enthusiastically investigate how a mammalian male germ cell commits to become a functional sperm. Our studies will therefore advance our understanding of sperm development and may suggest approaches to promote fertility.
