A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals

Tianxiong Yu; Adriano Biasini; Katharine Cecchini; Martin Saflund; Haiwei Mou; Amena Arif; Atiyeh Eghbali; Dirk de Rooij; Zhiping Weng; Phillip D Zamore; Deniz M Ozata

doi:10.1261/rna.079472.122

A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals

Tianxiong Yu, Adriano Biasini, Katharine Cecchini, Martin Saflund, Haiwei Mou, Amena Arif, Atiyeh Eghbali, Dirk de Rooij, Zhiping Weng, Phillip D Zamore, Deniz M Ozata

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	30-43
Number of pages	14
Journal	RNA
Volume	29
Issue number	1
Early online date	14 Oct 2022
DOIs	https://doi.org/10.1261/rna.079472.122
Publication status	Published - Jan 2023

Bibliographical note

Publisher Copyright:
© 2023 Cold Spring Harbor Laboratory Press. All rights reserved.

Funding

We thank S. Pechold, T. Giehl, B. Gosselin, Y. Gu, and T. Krumpoch at UMMS FACS Core for their expert mouse germ cell sorting; J. Gallant at the UMMS Transgenic Animal Modeling Core for help generating Tcfl5em1/em1 mutant mice; K. Orwig for providing rhesus macaque testis specimens; C. Baer for her expert help with Leica SP8 Lightning confocal microscopy; C. Tipping and C. Andersson for technical assistance; and members of the Zamore and Ozata laboratories for discussions and critical comments on the manuscript. This work was supported in part by National Institute of General Medical Sciences (NIGMS) grants R37 GM062862 and R35 GM136275 (P.D.Z.), National Institute of Child Health and Human Development (NICHD) grant P01 HD078253 (Z.W. and P.D.Z.), Swedish Research Council grant 2020-03818 (D.M.O.), and Carltryggersstiftelse CTS 21:1158 (D.M.O.). The UMMS FACS Core is supported in part by National Institutes of Health (NIH) grant S10OD028576.

Funders	Funder number
Carltryggersstiftelse	CTS 21:1158
National Institutes of Health	S10OD028576
National Institute of General Medical Sciences	R37 GM062862, R35 GM136275
National Institute of Child Health and Human Development	P01 HD078253
Vetenskapsrådet	2020-03818

Keywords

TCFL5
A-MYB
pachytene piRNAs
spermatogenesis

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10.1261/rna.079472.122Licence: CC BY

RNA-2023-Yu-30-43Final published version, 3.36 MBLicence: CC BY

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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.",

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A-MYB/TCFL5 regulatory architecture ensures the production of pachytene piRNAs in placental mammals

Abstract

Bibliographical note

Funding

Keywords

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