Piwi–piRNA complexes induce stepwise changes in nuclear architecture at target loci. (2nd August 2021)

• Record Type: Journal Article
• Authors: Iwasaki, Yuka W; Sriswasdi, Sira; Kinugasa, Yasuha; Adachi, Jun; Horikoshi, Yasunori; Shibuya, Aoi; Iwasaki, Wataru; Tashiro, Satoshi; Tomonaga, Takeshi; Siomi, Haruhiko
• Is Part Of: EMBO journal. Volume 40:Number 18(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-02
• Subjects: chromatin conformation -- heterochromatin formation -- nuclear localization -- RNA silencing -- transcriptional regulation; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2021108345
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: PIWI‐interacting RNAs (piRNAs) are germline‐specific small RNAs that form effector complexes with PIWI proteins (Piwi–piRNA complexes) and play critical roles for preserving genomic integrity by repressing transposable elements (TEs). Drosophila Piwi transcriptionally silences specific targets through heterochromatin formation and increases histone H3K9 methylation (H3K9me3) and histone H1 deposition at these loci, with nuclear RNA export factor variant Nxf2 serving as a co‐factor. Using ChEP and DamID‐seq, we now uncover a Piwi/Nxf2‐dependent target association with nuclear lamins. Hi‐C analysis of Piwi or Nxf2‐depleted cells reveals decreased intra‐TAD and increased inter‐TAD interactions in regions harboring Piwi–piRNA target TEs. Using a forced tethering system, we analyze the functional effects of Piwi–piRNA/Nxf2‐mediated recruitment of piRNA target regions to the nuclear periphery. Removal of active histone marks is followed by transcriptional silencing, chromatin conformational changes, and H3K9me3 and H1 association. Our data show that the Piwi–piRNA pathway can induce stepwise changes in nuclear architecture and chromatin state at target loci for transcriptional silencing. SYNOPSIS: Piwi–piRNA‐mediated transcriptional silencing of transposable elements is required to maintain genomic integrity. Here, stepwise heterochromatin‐structure formation is found to also involve Piwi–piRNA‐mediated nuclear architecture changes at target regions. Piwi recruits chromatin regions containing piRNA targets to the nuclear periphery. Piwi increases intra‐TAD interactions and decreases inter‐TAD interactions at piRNA target loci. Nxf2 is essential for Piwi‐mediated localization of targets to the nuclear periphery. Spatial regulation of piRNA targets triggers stepwise formation of heterochromatin structure. Abstract : Formation of heterochromatin structure at piRNA target loci involves their Piwi/Nxf2‐dependent recruitment to the nuclear periphery.