title: An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes.
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 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 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 feedforward 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.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Xin Zhiguo
authors.initials: XZ
authors.lastname: Li
authors.forename: Christian K
authors.initials: CK
authors.lastname: Roy
authors.forename: Xianjun
authors.initials: X
authors.lastname: Dong
authors.forename: Ewelina
authors.initials: E
authors.lastname: Bolcun-Filas
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Bo W
authors.initials: BW
authors.lastname: Han
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Moore
authors.forename: John C
authors.initials: JC
authors.lastname: Schimenti
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Zamore
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000172:deficiency / Q000235:genetics; D005075:Biological Evolution; D002645:Chickens; D004706:Endodeoxyribonucleases / Q000172:deficiency / Q000235:genetics; D025461:Feedback, Physiological; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D008297:Male; D008540:Meiosis; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049471:Pachytene Stage; D010641:Phenotype; D020598:Proto-Oncogene Proteins c-myb / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000096:biosynthesis*; D013091:Spermatogenesis; D013737:Testis / Q000254:growth & development / Q000378:metabolism*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D060565:Argonaute Proteins; D004706:Endodeoxyribonucleases; D020598:Proto-Oncogene Proteins c-myb; D034741:RNA, Small Interfering; D015534:Trans-Activators; D000099257:Meiotic Recombination Protein SPO11; C490283:Mybl1 protein, mouse; C448522:Piwil1 protein, mouse