A heterochromatin-dependent transcription machinery drives piRNA expression

• Published in: Nature (London) Vol. 549; no. 7670; pp. 54 - 59
• Main Authors: Andersen, Peter Refsing, Tirian, Laszlo, Vunjak, Milica, Brennecke, Julius
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.09.2017; Nature Publishing Group
• Subjects: 38; 38/15; 38/32; 38/39; 38/89; 38/91; 45; 45/15; 45/91; 631/337/100; 631/337/384/521; 631/337/572; 64; 64/24; Animals; Biosynthesis; Chromosomal Proteins, Non-Histone - metabolism; Clusters; Complex formation; Deoxyribonucleic acid; DNA; DNA methylation; DNA Transposable Elements - genetics; DNA-directed RNA polymerase; Drosophila; Drosophila melanogaster - genetics; Drosophila Proteins - metabolism; Evolution; Female; Fruit flies; Gene expression; Gene loci; Gene Silencing; Genetic aspects; Genetic research; Genomes; Genomics; Gonads; Heterochromatin; Heterochromatin - chemistry; Heterochromatin - genetics; Heterochromatin - metabolism; Humanities and Social Sciences; Initiation complex; Insects; Methods; multidisciplinary; Multigene Family - genetics; Nucleotide sequence; Physiological aspects; Promoter Regions, Genetic - genetics; Proteins; Ribonucleic acid; RNA; RNA polymerase; RNA polymerase II; RNA Polymerase II - chemistry; RNA Polymerase II - metabolism; RNA, Small Interfering - biosynthesis; RNA, Small Interfering - genetics; Science; TATA-binding protein; Telomere-binding protein; Telomeric Repeat Binding Protein 2 - metabolism; TFIID protein; Transcription (Genetics); Transcription Factor TFIIA - metabolism; Transcription factors; Transcription initiation factor TFIIA; Transcription Initiation, Genetic; Transcription, Genetic; Transposons; TRF2 protein
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature23482

Nuclear small RNA pathways safeguard genome integrity by establishing transcription-repressing heterochromatin at transposable elements. This inevitably also targets the transposon-rich source loci of the small RNAs themselves. How small RNA source loci are efficiently transcribed while transposon promoters are potently silenced is not understood. Here we show that, in Drosophila , transcription of PIWI-interacting RNA (piRNA) clusters—small RNA source loci in animal gonads—is enforced through RNA polymerase II pre-initiation complex formation within repressive heterochromatin. This is accomplished through Moonshiner, a paralogue of a basal transcription factor IIA (TFIIA) subunit, which is recruited to piRNA clusters via the heterochromatin protein-1 variant Rhino. Moonshiner triggers transcription initiation within piRNA clusters by recruiting the TATA-box binding protein (TBP)-related factor TRF2, an animal TFIID core variant. Thus, transcription of heterochromatic small RNA source loci relies on direct recruitment of the core transcriptional machinery to DNA via histone marks rather than sequence motifs, a concept that we argue is a recurring theme in evolution. Transcription of Drosophila PIWI-interacting RNA (piRNA) clusters is enforced through RNA polymerase II pre-initiation complex formation within repressive heterochromatin, accomplished through the transcription factor IIA subunit paralogue Moonshiner. Initiating transcription in silent chromatin The PIWI-interacting RNA (piRNA) pathway is important for genome stability in the germline by establishing repressive heterochromatin at transposons. How piRNAs are transcribed from their loci within transposons that are transcriptionally silenced is not understood. Here Julius Brennecke and colleagues show that transcription initiation of Drosophila piRNA precursors involves a germline-specific TFIIA-L paralogue which they name Moonshiner. This protein is recruited to piRNA clusters in heterochromatin via an HP1 paralogue, Rhino, and couples to the core RNA polymerase II transcription machinery. Moonshiner therefore enables active piRNA transcription in a repressive heterochromatin environment.