Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MIWI2 and MILI have differential effects on piRNA biogenesis and DNA methylation

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Sergei Manakov

PROVIDER: E-GEOD-70731 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing.

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

piRNA pathway targets active LINE1 elements to establish repressive H3K9me3 mark in germ cells

Project description:Transposable elements (TEs) occupy large fraction of metazoan genomes and pose constant threat to genomic integrity. This threat is particularly critical in germ cells, as changes in the genome that are induced by TEs will be transmitted to the next generation. Small non-coding piwi interacting (pi)RNAs recognize and silence a diverse set of TEs in germ cells. In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown. Here we show that in addition to DNA methylation, the piRNA pathway is required to maintain a high level of the repressive H3K9me3 histone modification on long interspersed nuclear elements (LINEs) in germ cells. piRNA-dependent chromatin repression targets exclusively full-length elements of actively transposing LINE families, demonstrating the remarkable ability of the piRNA pathway to recognize active elements among the large number of genomic transposon fragments. Total of 34 libraries were analyzed. In case of ChIP libraries, every 'input' sample was used for normalization of the respective ChIP (H3K9me3 or H3) sample; the input libraries preceed ChIP libraries in the list below. There are four replicates (input-ChIP pairs) for H3K9me3 ChIP on liver cells, two for ChIP on testicular somatic cells for each genotype (Miwi2 Het and KO); and four for ChIP on male germ cells for each genotype (one from FACS-sorted germ cells, and three from MACS-sorted germ cells). Each replicate has a Het/KO pair, and the respective libraries were cloned from the material isolated from littermates. One H3 ChIP for each genotype is included, with respective inputs.

2014-06-13 | E-GEOD-58332 | biostudies-arrayexpress

SPOCD1 is a novel executor of piRNA-directed DNA methylation that links MIWI2 to the de novo DNA methylation machinery

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

C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germline

Project description:In the male mouse germline, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide the DNA methylation of young active transposable elements (TEs) through SPOCD1. We identified loss-of-function variants in human SPOCD1 that cause male infertility and defective TE silencing. One SPOCD1 pathogenic allele encodes a truncated protein that lacks the conserved carboxy-terminus. We demonstrated that this deleted region interacts with C19ORF84. In mouse foetal germ cells, the nuclear protein C19ORF84 is required for the association of SPOCD1 with DNMT3L, an essential component of the de novo methylation machinery. In summary, we identified a conserved role for SPOCD1 in safeguarding the continuity of the human germline and discovered C19ORF84, an uncharacterised protein essential for 15 orchestrating piRNA-directed DNA methylation.

2024-02-13 | E-MTAB-11612 | biostudies-arrayexpress

MIWI2 and MILI have differential effects on piRNA biogenesis and DNA methylation

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

Tissue- and plasma-derived exosomal protein biomarkers define multiple human cancers

Project description:There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of exosomes in 426 human samples from tissue explants (TE), plasma and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, HSP90AB1 represent pan-exosomes/exomeres. Moreover, we identified novel pan-exosome/exomere markers (e.g., ACTB, MSN, RAP1B). As proof of principle that exosomes are ideal diagnostic tools, we analyzed the proteome of TE exosomes (n=151) or plasma-derived exosomes (n=120). Comparison of TE exosomes identified proteins (e.g., VCAN, TNC, THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machinelearning classification of plasma-derived exosomes revealed 95% sensitivity/90% specificity in identifying cancer-associated exosomes. Finally, we defined a panel of tumor-type specific exosomal proteins in TE and plasma, which may help classify tumors of unknown primary origin. Overall, exosomal proteins can serve as reliable biomarkers for cancer detection and for determining cancer type

2020-08-17 | PXD018301 | Pride

SPOCD1 is a novel executor of piRNA-directed DNA methylation that links MIWI2 to the de novo DNA methylation machiner

2020-06-22 | PXD016701 | Pride

SPOCD1 is a novel executor of piRNA-directed DNA methylation that links MIWI2 to the de novo DNA methylation machinery

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

TEX15 is an essential executor of MIWI2-directed transposon DNA methylation and silencing.

2020-06-18 | PXD019087 | Pride

Differences in DNA Methylation between Human Neuronal and Glial Cells are Concentrated in Enhancers and non-CpG Sites [Enhanced Reduced Representation Bisulfite Sequencing data]

Project description:We applied Illumina Human Methylation450K array to perform a genomic-scale single-site resolution DNA methylation analysis in neuronal and nonneuronal (primarily glial) nuclei separated from the orbitofrontal cortex of postmortem human brain. The findings were validated using enhanced reduced representation bisulfite sequencing. We identified thousands of sites differentially methylated (DM) between neuronal and nonneuronal cells. The DM sites were depleted within CpG islandM-bM-^@M-^Scontaining promoters but enriched in predicted enhancers. Classification of the DM sites into those undermethylated in neurons (neuronal type) and those undermethylated in nonneuronal cells (glial type), combined with findings of others that methylation within control elements typically negatively correlates with gene expression, yielded large sets of predicted neuron-specific and nonneuron-specific genes. These sets of predicted genes were in excellent agreement with the available direct measurements of gene expression in human and mouse. We also found a distinct set of DNA methylation patterns that were unique for neuronal cells. In particular, neuronal-type differential methylation was overrepresented in CpG island shores, enriched within gene bodies but not in intergenic regions, and preferentially harbored binding motifs for a distinct set of transcription factors, including neuron-specific activity-dependent factors. Finally, non-CpG methylation was substantially more prevalent in neurons than in nonneuronal cells. Extended Reduced Representation Bisulfite Sequencing (ERRBS) was performed on genomic DNA to validate the Infinium HM450K DNA methylation data (Kozlenkov et. al., 2013, Nucleic Acids Research, accepted for publication).

2013-09-14 | E-GEOD-50852 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data