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

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

Author information

1
Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: li-quan.zhou@nih.gov.
2
Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
3
NINDS Flow Cytometry Core Facility, National Institutes of Health, Bethesda, MD 20892, USA.
4
Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jurrien.dean@nih.gov.

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.

KEYWORDS:

BTBD18; male sterility; pachytene; piRNA; piRNA biogenesis; piRNA-generating loci; round spermatid; spermatogenesis; spermiogenesis

PMID:
28292424
DOI:
10.1016/j.devcel.2017.02.007
[Indexed for MEDLINE]
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