Expression-inheritance
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR668748.fastq.gz | Fastqsanger.gz | |||
| ERR668749.fastq.gz | Fastqsanger.gz | |||
| ERR668750.fastq.gz | Fastqsanger.gz | |||
| ERR668751.fastq.gz | Fastqsanger.gz | |||
| ERR668752.fastq.gz | Fastqsanger.gz |
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Project description:Natural variation in protein expression is common in all organisms and contribute to phenotypic differences among individuals. While variation in gene expression at the transcript level has been extensively investigated, the genetic mechanisms underlying variation in protein expression have lagged considerably behind. Here we investigate genetic architecture of protein expression by profiling a deep mouse brain proteome of two inbred strains, C57BL/6J (B6) and DBA/2J (D2), and their reciprocal F1 hybrids using two-dimensional liquid chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) technology. By comparing protein expression levels in the four mouse strains, we observed 329 statistically significant differentially expressed proteins between the two parental strains and identified four common inheritance patterns, including dominant, additive, over- and under-dominant expression. We further applied the proteogenomic approach to detect variant peptides and define protein allele-specific expression (pASE).
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Project description:Transgenerational epigenetic inheritance (TEI) describes the transmission of gene-regulatory information across generations without altering DNA sequences. TEI allows priming of offspring towards changing environmental conditions and plays a role in the maintenance of gene silencing of selfish genetic elements like transposons. Small regulatory RNAs are well known to act in TEI, and can be transmitted via the male. Such inheritance via sperm requires dedicated mechanisms, as much of the cellular content is extruded during spermatogenesis. We identify a phase separation-based mechanism, which couples the paternal inheritance of a specific small RNA-bound silencing factor via S-palmitoylation to the transport of membranous organelles. Our findings uncover a thus far unknown paternal TEI mechanism, and describe a novel mode of transport of phase-separated condensates.
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Project description:Gene silencing mediated by dsRNA (RNAi) can persist for multiple generations in C. elegans (termed RNAi inheritance). Here we describe the results of a forward genetic screen in C. elegans that has identified six factors required for RNAi inheritance: GLH-1/VASA, PUP-1/CDE-1, MORC-1, SET-32, and two novel nematode-specific factors that we term here (heritable RNAi defective) HRDE-2 and HRDE-4. The new RNAi inheritance factors exhibit mortal germline (Mrt) phenotypes, which we show is likely caused by epigenetic deregulation in germ cells. We also show that HRDE-2 contributes to RNAi inheritance by facilitating the binding of small RNAs to the inheritance Argonaute (Ago) HRDE-1. Together, our results identify additional components of the RNAi inheritance machinery whose sequence conservation provides insights into the molecular mechanism of RNAi inheritance, further our understanding of how the RNAi inheritance machinery promotes germline immortality, and show that HRDE-2 couples the inheritance Ago HRDE-1 with the small RNAs it needs to direct RNAi inheritance and germline immortality.
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