BTBD18 Regulates a Subset of piRNA-Generating Loci through Transcription Elongation in Mice

Publication date: 13 March 2017
Source:Developmental Cell, Volume 40, Issue 5
Author(s): Liquan Zhou, Bertram Canagarajah, Yangu Zhao, Boris Baibakov, Keizo Tokuhiro, Dragan Maric, Jurrien Dean
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.

Graphical abstract

Teaser

piRNAs are small non-coding RNAs primarily expressed in animal gonads. Zhou et al. implicate BTBD18, a nuclear protein, in piRNA biogenesis as key for male fertility. BTBD18 binds to a subset of pachytene piRNA-producing loci in mouse testes, promotes transcription elongation, and promotes piRNA precursor expression for successful germ cell development.


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