BTBD18 通过转录延伸调控小鼠中一组 piRNA 生成基因座。

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

机构信息

Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Dev Cell. 2017 Mar 13;40(5):453-466.e5. doi: 10.1016/j.devcel.2017.02.007.

DOI:10.1016/j.devcel.2017.02.007

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.

摘要

PIWI 相互作用 RNA（piRNA）是动物生殖细胞发育所必需的小非编码 RNA。尽管对转录后加工进行了深入研究，但哺乳动物中 piRNA 生物发生的染色质调节剂在很大程度上仍未得到探索。在这里，我们记录了 BTBD18 是小鼠睾丸中减数分裂前期的核蛋白，它占据了减数分裂前期产生 piRNA 的基因座的一部分。在小鼠中敲除 Btbd18 会破坏 piRNA 的生物发生，阻止精子发生，并导致雄性不育。转录组谱分析、染色质可及性和 RNA 聚合酶 II 占据表明，BTBD18 通过促进转录延伸来促进减数分裂前期 piRNA 前体的表达。因此，我们的研究确定 BTBD18 是通过 RNA 聚合酶 II 延伸在基因组 piRNA 基因座的一部分上激活转录的特定控制器。