title: BTBD18 Regulates a Subset of piRNA-Generating Loci through Transcription Elongation in Mice.
abstract: PIWI-interacting RNAs (piRNAs) are small non-coding RNAs essential for animal germ cell development. Despite intense investigation of post-transcriptional processing, chromatin regulators for piRNA biogenesis in mammals remain largely unexplored. Here we document that BTBD18 is a pachytene nuclear protein in mouse testes that occupies a subset of pachytene piRNA-producing loci. Ablation of Btbd18 in mice disrupts piRNA biogenesis, prevents spermiogenesis, and results in male sterility. Transcriptome profiling, chromatin accessibility, and RNA polymerase II occupancy demonstrate that BTBD18 facilitates expression of pachytene piRNA precursors by promoting transcription elongation. Thus, our study identifies BTBD18 as a specific controller for transcription activation through RNA polymerase II elongation at a subset of genomic piRNA loci.
authors.affiliation: Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: li-quan.zhou@nih.gov.
authors.forename: Liquan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Bertram
authors.initials: B
authors.lastname: Canagarajah
authors.affiliation: Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yangu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Baibakov
authors.affiliation: Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Keizo
authors.initials: K
authors.lastname: Tokuhiro
authors.affiliation: NINDS Flow Cytometry Core Facility, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Dragan
authors.initials: D
authors.lastname: Maric
authors.affiliation: Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jurrien.dean@nih.gov.
authors.forename: Jurrien
authors.initials: J
authors.lastname: Dean
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D017353:Gene Deletion; D056426:Genetic Loci; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics; D013737:Testis / Q000166:cytology; D061805:Transcription Elongation, Genetic
chemical_list: C000620806:BTBD18 protein, mouse; D009687:Nuclear Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: BTBD18; male sterility; pachytene; piRNA; piRNA biogenesis; piRNA-generating loci; round spermatid; spermatogenesis; spermiogenesis