Publications by authors named "P Deininger"
Background: Endogenous expression of L1 mRNA is the first step in an L1-initiated mutagenesis event. However, the contribution of individual cell types to patterns of organ-specific L1 mRNA expression remains poorly understood, especially at single-locus resolution. We introduce a method to quantify expression of mobile elements at the single-locus resolution in scRNA-Seq datasets called Single Cell Implementation to Find Expressed Retrotransposons (SCIFER).
View Article and Find Full Text PDFOnly a select few L1 loci in the human genome are expressed in any given cell line or organ, likely to minimize damage done to the genome. The epigenetic features and requirements of expressed L1 loci are currently unknown. Using human cells and comprehensive epigenetic analysis of individual expressed and unexpressed L1 loci, we determined that endogenous L1 transcription depends on a combination of epigenetic factors, including open chromatin, activating histone modifications, and hypomethylation at the L1 promoter.
View Article and Find Full Text PDFExpression of L1 mRNA, the first step in the L1 copy-and-paste amplification cycle, is a prerequisite for L1-associated genomic instability. We used a reported stringent bioinformatics method to parse L1 mRNA transcripts and measure the level of L1 mRNA expressed in mouse and rat organs at a locus-specific resolution. This analysis determined that mRNA expression of L1 loci in rodents exhibits striking organ specificity with less than 0.
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- Alu elements are common in the human genome and play a significant role in causing genetic instability, particularly during DNA double-stranded breaks due to their high copy number and characteristics that affect recombination.
- Using a reporter-gene assay, the study reveals that mismatches between Alu elements can lead to two main outcomes: either nonallelic homologous recombination (HR) or DNA breaks that can cause deletions through alternative repair processes.
- The formation of these intermediates is dependent on RAD52, and the presence of defects in DNA repair genes like ERCC1 and MSH2 influences the types of deletions associated with Alu elements, which may contribute to different cancer types.
Article Synopsis
- Retrotransposons, especially the L1 element, significantly influence mammalian genomes and human diseases, comprising 17% of the human genome despite most having defects.
- The study tested RNA-Seq data from prostate cancer cells to compare the quality and effort required for identifying expressed L1, finding minimal data loss with whole-cell, strand-specific RNA-Seq compared to cytoplasmic RNA-Seq, though it required more manual curation.
- The research concludes that with careful manual curation, both cytoplasmic and whole-cell stranded RNA-Seq datasets can effectively identify expressed L1 loci, even though non-strand-specific datasets result in significant data loss.