Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

An Ancient Transcription Factor An Ancient Transcription Factor During Early Meiosis in Mouse Testes (PAS-Seq and CAGE)

ABSTRACT: Animal germ cells produce PIWI-interacting RNAs (piRNAs), small silencing RNAs that suppress transposons and enable gamete maturation. Mammalian transposon-silencing piRNAs accumulate early in spermatogenesis, whereas pachytene piRNAs are produced later during post-natal spermatogenesis and account for >95% of all piRNAs in the adult mouse testis. Mutants defective for pachytene piRNA pathway proteins fail to produce mature sperm, but neither the piRNA precursor transcripts nor the trigger for pachytene piRNA production is known. Here, we show that the transcription factor A-MYB initiates pachytene piRNA production. A-MYB drives transcription of both pachytene piRNA precursor RNAs and the mRNAs for core piRNA biogenesis factors, including MIWI, the protein through which pachytene piRNAs function. A-MYB regulation of piRNA pathway proteins and piRNA genes creates a coherent feed-forward loop that ensures the robust accumulation of pachytene piRNAs. This regulatory circuit, which can be detected in rooster testes, likely predates the divergence of birds and mammals. PAS-Seq and CAGE in mouse testes

ORGANISM(S): Mus musculus

SUBMITTER: Christian Roy

PROVIDER: E-GEOD-45048 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes.

Li Xin Zhiguo XZ Roy Christian K CK Dong Xianjun X Bolcun-Filas Ewelina E Wang Jie J Han Bo W BW Xu Jia J Moore Melissa J MJ Schimenti John C JC Weng Zhiping Z Zamore Phillip D PD

Molecular cell 20130321 1

Animal germ cells produce PIWI-interacting RNAs (piRNAs), small silencing RNAs that suppress transposons and enable gamete maturation. Mammalian transposon-silencing piRNAs accumulate early in spermatogenesis, whereas pachytene piRNAs are produced later during postnatal spermatogenesis and account for >95% of all piRNAs in the adult mouse testis. Mutants defective for pachytene piRNA pathway proteins fail to produce mature sperm, but neither the piRNA precursor transcripts nor the trigger for pa ...[more]

PMID: 23523368

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Project description:In the mammalian testis, the pool of spermatogonia is amplified by mitosis before these progenitor germ cells undergo meiosis to generate the haploid cells that give rise to sperm. Extensive changes in the transcriptome accompany the onset of the pachytene stage of meiosis, including the transcriptional activation of meiotic genes, the pachytene piRNA pathway, as well as mRNAs required later during spermiogenesis. How transcription is regulated to ensure the precise timing of this major reprogramming of gene expression remains largely uncharacterized. Here, we report that the testis-specific transcription factor TCFL5 is initially activated by the transcription factor A-MYB during meiosis. Subsequently, A-MYB and TCFL5 mutually reinforce their own transcription establishing a central regulatory circuit that regulates meiosis and spermiogenesis, as well as mediates pachytene piRNA production. TCFL5 drives the transcription of 476 genes required for meiosis including genes encoding pachytene piRNA biogenesis proteins, and 796 genes required for spermiogenesis. Tcfl5−/− mutant mice are sterile and spermatogenesis arrests at the mid- or late-pachytene stage of meiosis. Intriguingly, Tcfl5 haploinsufficiency leads to reduced male fertility suggesting germ cells are sensitive to Tcfl5 dosage to develop. Compromised TCFL5 expression underlies the reduced fertility phenotype directly or indirectly through regulating other transcription factors in Tcfl5+/− mutant mice. TCFL5 drives the transcription of evolutionarily younger pachytene piRNAs, while A-MYB regulates older pachytene piRNAs. Older and younger piRNAs mutually initiate their own processing providing evidence how these selfish genetic elements hijack meiotic transcriptional network to amplify themselves. We also demonstrate that TCFL5-mediated regulation of male meiosis and piRNA production is conserved in macaque. Our data establish a direct role of TCFL5 in ensuring the simultaneous activation of genes required for meiosis and spermiogenesis in mammals.

Dataset Information

An Ancient Transcription Factor An Ancient Transcription Factor During Early Meiosis in Mouse Testes (PAS-Seq and CAGE)

Publications

An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes.

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