A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals
- Tiangxiong Yu1,6,
- Adriano Biasini2,6,
- Katharine Cecchini2,6,
- Martin Säflund3,
- Haiwei Mou4,
- Amena Arif2,7,
- Atiyeh Eghbali3,
- Dirk G. de Rooij5,
- Zhiping Weng1,
- Phillip D. Zamore2 and
- Deniz M. Özata3
- 1Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
- 2RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
- 3Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden
- 4Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
- 5Reproductive Biology Group, Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht 3584, the Netherlands
- Corresponding authors: phillip.zamore{at}umassmed.edu, deniz.ozata{at}su.se
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↵6 These authors contributed equally to this work.
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.
Keywords
- Received October 6, 2022.
- Accepted October 7, 2022.
This article, published in RNA, is available undera Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
