SPOCD1 is a novel executor of piRNA-directed DNA methylation that links MIWI2 to the de novo DNA methylation machinery
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ABSTRACT:
PROVIDER: PRJEB35332 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3654670_1.fastq.gz | Fastqsanger.gz | |||
| ERR3654670_2.fastq.gz | Fastqsanger.gz | |||
| ERR3654680_1.fastq.gz | Fastqsanger.gz | |||
| ERR3654680_2.fastq.gz | Fastqsanger.gz | |||
| ERR3654690_1.fastq.gz | Fastqsanger.gz |
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Project description:In mammals, the acquisition of the germline from the soma provides the germline with an essential challenge, the necessity to erase and reset genomic methylation. In the male germline RNA-directed DNA methylation silences young active transposable elements (TEs). The PIWI protein MIWI2 (PIWIL4) and its associated PIWI-interacting RNAs (piRNAs) are proposed to tether MIWI2 to nascent TE transcripts and instruct DNA methylation. The mechanism by which MIWI2 directs de novo TE methylation is poorly understood but central to the immortality of the germline. Here, we define the interactome of MIWI2 in foetal gonocytes that are undergoing de novo genome methylation and identify a novel MIWI2-associated factor, SPOCD1, that is essential for young TE methylation and silencing. The loss of Spocd1 in mice results in male specific infertility and does not impact on piRNA biogenesis nor localization of MIWI2 to the nucleus. SPOCD1 is a nuclear protein and its expression is restricted to the period of de novo genome methylation. We found SPOCD1 co-purified in vivo with DNMT3L and DNMT3A, components of the de novo methylation machinery as well as constituents of the NURD and BAF chromatin remodelling complexes. We propose a model whereby tethering of MIWI2 to a nascent TE transcript recruits repressive chromatin remodelling activities and the de novo methylation apparatus through its association with SPOCD1. In summary, we have identified a novel and essential executor of mammalian piRNA-directed DNA methylation.
2020-06-22 | PXD016701 | Pride
Project description:In mammals, the acquisition of the germline from the soma provides the germline with an essential challenge, the necessity to erase and reset genomic methylation. De novo genome methylation re-encodes the epigenome including transposable element (TE) silencing. In the male germline RNA-directed DNA methylation silences young active TEs. The PIWI protein MIWI2 (PIWIL4) and its associated PIWI-interacting RNA (piRNAs) act to tether MIWI2 to nascent TE transcripts and instruct DNA methylation of the active TE. The mechanism by which MIWI2 directs de novo TE methylation is poorly understood but central to the immortality of the germline. Here, we define the interactome of MIWI2 in fetal gonocytes that are undergoing de novo genome methylation and identify a novel MIWI2-associated factor SPOCD1 that is essential for TE silencing. The loss of Spocd1 in mice phenocopies that of Miwi2-deficient mice and does not impact on piRNA biogenesis nor localization of MIWI2 to the nucleus. SPOCD1 is a nuclear protein and its expression is restricted to the period of de novo genome methylation. We found SPOCD1 co-purified in vivo with constituents of several repressive chromatin remodelling complexes (NURD and BAF) as well as DNMT3L and DNMT3A, components of the de novo methylation machinery. We propose a model whereby tethering of MIWI2 to a nascent TE transcript recruits repressive chromatin remodelling activities and the de novo methylation apparatus through its association with SPOCD1. In summary, we have identified a novel and essential executor of mammalian piRNA-directed DNA methylation.
2020-06-17 | GSE131377 | GEO
Project description:In mammals, the acquisition of the germline from the soma provides the germline with an essential challenge, the necessity to erase and reset genomic methylation. In the male germline RNA-directed DNA methylation silences young active transposable elements (TEs). The PIWI protein MIWI2 (PIWIL4) and its associated PIWI-interacting RNAs (piRNAs) are proposed to tether MIWI2 to nascent TE transcripts and instruct DNA methylation. The mechanism by which MIWI2 directs de novo TE methylation is poorly understood but central to the immortality of the germline. Here, we define the interactome of MIWI2 in foetal gonocytes that are undergoing de novo genome methylation and identify a novel MIWI2-associated factor, SPOCD1, that is essential for young TE methylation and silencing. The loss of Spocd1 in mice results in male specific infertility and does not impact on piRNA biogenesis nor localization of MIWI2 to the nucleus. SPOCD1 is a nuclear protein and its expression is restricted to the period of de novo genome methylation. We found SPOCD1 co-purified in vivo with DNMT3L and DNMT3A, components of the de novo methylation machinery as well as constituents of the NURD and BAF chromatin remodelling complexes. We propose a model whereby tethering of MIWI2 to a nascent TE transcript recruits repressive chromatin remodelling activities and the de novo methylation apparatus through its association with SPOCD1. In summary, we have identified a novel and essential executor of mammalian piRNA-directed DNA methylation.
2020-06-01 | E-MTAB-7997 | biostudies-arrayexpress
Project description:The PIWI protein MIWI2 and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of young active transposable elements (TEs) in the male germline. Here we show that MIWI2 associates with TEX15 in foetal gonocytes. TEX15 is predominantly a nuclear protein that is not required for piRNA biogenesis but is essential for piRNA-directed TE de novo methylation and silencing. In summary, TEX15 is an essential executor of mammalian piRNA-directed DNA methylation.
2020-06-18 | PXD019087 | Pride
Project description:SPOCD1 is a novel executor of piRNA-directed DNA methylation that links MIWI2 to the de novo DNA methylation machinery
| PRJNA543424 | ENA
Project description:The PIWI protein MIWI2 and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of young active transposable elements (TEs) in the male germline. Here we show that MIWI2 associates with TEX15 in foetal gonocytes. TEX15 is predominantly a nuclear protein that is not required for piRNA biogenesis but is essential for piRNA-directed TE de novo methylation and silencing. In summary, TEX15 is an essential executor of mammalian piRNA-directed DNA methylation.
2020-06-17 | GSE150350 | GEO
Project description:The PIWI protein MIWI2 and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of young active transposable elements (TEs) in the male germline. Here we show that MIWI2 associates with TEX15 in foetal gonocytes. TEX15 is predominantly a nuclear protein that is not required for piRNA biogenesis but is essential for piRNA-directed TE de novo methylation and silencing. In summary, TEX15 is an essential executor of mammalian piRNA-directed DNA methylation.
2020-06-17 | E-MTAB-9090 | biostudies-arrayexpress
Project description:In developing male germ cells, prospermatogonia, two Piwi proteins, MILI and MIWI2, use piRNA guides to repress transposable element (TE) expression and ensure genome stability and proper gametogenesis. In addition to their roles in post-transcriptional TE repression, both proteins are required for DNA methylation of TE sequences. Here we analyzed the effect of Miwi2 deficiency on piRNA biogenesis and transposon repression. Miwi2-deficiency had only a minor impact on piRNA biogenesis; however, the piRNA profile of Miwi2-knockout mice indicated overexpression of several LINE1 TE families that led to activation of the ping-pong piRNA cycle. Furthermore, we found that MILI and MIWI2 have distinct functions in TE repression in the nucleus. MILI is responsible for DNA methylation of a larger subset of TE families than MIWI2 suggesting that the proteins have independent roles in establishing DNA methylation patterns.
2015-07-11 | GSE70731 | GEO
Project description:In developing male germ cells, prospermatogonia, two Piwi proteins, MILI and MIWI2, use piRNA guides to repress transposable element (TE) expression and ensure genome stability and proper gametogenesis. In addition to their roles in post-transcriptional TE repression, both proteins are required for DNA methylation of TE sequences. Here we analyzed the effect of Miwi2 deficiency on piRNA biogenesis and transposon repression. Miwi2-deficiency had only a minor impact on piRNA biogenesis; however, the piRNA profile of Miwi2-knockout mice indicated overexpression of several LINE1 TE families that led to activation of the ping-pong piRNA cycle. Furthermore, we found that MILI and MIWI2 have distinct functions in TE repression in the nucleus. MILI is responsible for DNA methylation of a larger subset of TE families than MIWI2 suggesting that the proteins have independent roles in establishing DNA methylation patterns. Small RNA profiles (19-30 nt range) of embryonic (E16.5) and post-natal (P10) testis of Miwi2 mutant mice and matched heterozygote controls. mRNA profiles of embryonic testis (E16.5) of heterozygote control mice and of postnatal testis (P10) of Miwi2 and Mili mutants and heterozygote controls. CpG methylation BS-seq profile of postnatal (P10) spermatocytes of Miwi2 mutant mice and matched heterozygote controls.
2015-07-11 | E-GEOD-70731 | biostudies-arrayexpress
Project description:The PIWI-interacting RNA (piRNA) pathway guides the DNA methylation of young active transposons during male mouse germline development. piRNAs tether the PIWI protein MIWI2 (PIWIL4) to the nascent transposon transcript that results in DNA methylation through SPOCD1. Transposon methylation requires exacting precision: all copies need to be methylated yet, at the same time, off-target methylation must be avoided. However, the underlying mechanisms that ensure this precision remain unknown. Here, we show that SPOCD1 directly interacts with SPIN1, a chromatin reader that primarily binds H3K4me3 and this association is augmented by H3K9me3. The prevailing assumption is that all molecular events required for piRNA-directed DNA methylation occur after the engagement of MIWI2. Interestingly, we find that SPIN1 expression precedes that of both SPOCD1 and MIWI2. Furthermore, we demonstrate that young LINE1s, but not old copies are marked by H3K4me3 and H3K9me3 prior to the initiation of piRNA-directed DNA methylation. We generated a Spocd1 separation-of-function allele in the mouse that encodes a SPOCD1 variant that no longer interacts with SPIN1. We found that the SPOCD1-SPIN1 interaction is essential for spermatogenesis and piRNA-directed DNA methylation of young LINE1 elements. We propose that young LINE1 elements require a two-factor authentication process for DNA methylation, the first being the recruitment of SPIN1-SPOCD1 to licence the locus and the second is MIWI2 engagement with the nascent transcript, which is the trigger for methylation. In summary, independent events that licence, and trigger methylation underpin the basis of precision.
2024-09-04 | PXD041214 | Pride