Publications by authors named "Rebecca V Berrens"

The PIWI-interacting RNA (piRNA) pathway guides the DNA methylation of young, active transposons during germline development in male mice. piRNAs tether the PIWI protein MIWI2 (PIWIL4) to the nascent transposon transcript, resulting in DNA methylation through SPOCD1 (refs. ).

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Transposable elements (TEs) are highly expressed in preimplantation development. Preimplantation development is the phase when the cells of the early embryo undergo the first cell fate choice and change from being totipotent to pluripotent. A range of studies have advanced our understanding of TEs in preimplantation, as well as their epigenetic regulation and functional roles.

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In the male mouse germ line, PIWI-interacting RNAs (piRNAs), bound by the PIWI protein MIWI2 (PIWIL4), guide DNA methylation of young active transposons through SPOCD1. However, the underlying mechanisms of SPOCD1-mediated piRNA-directed transposon methylation and whether this pathway functions to protect the human germ line remain unknown. We identified loss-of-function variants in human SPOCD1 that cause defective transposon silencing and male infertility.

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The RNA-binding protein polypyrimidine tract binding protein 1 (PTBP1) has been found to have roles in CD4 T-cell activation, but its function in CD8 T cells remains untested. We show it is dispensable for the development of naïve mouse CD8 T cells, but is necessary for the optimal expansion and production of effector molecules by antigen-specific CD8 T cells in vivo. PTBP1 has an essential role in regulating the early events following activation of the naïve CD8 T cell leading to IL-2 and TNF production.

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Transposable elements (TEs) regulate diverse biological processes, from early development to cancer. Expression of young TEs is difficult to measure with next-generation, single-cell sequencing technologies because their highly repetitive nature means that short complementary DNA reads cannot be unambiguously mapped to a specific locus. Single CELl LOng-read RNA-sequencing (CELLO-seq) combines long-read single cell RNA-sequencing with computational analyses to measure TE expression at unique loci.

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The PIWI protein MIWI2 and its associated PIWI-interacting RNAs (piRNAs) instruct DNA methylation of young active transposable elements (TEs) in the male germline. piRNAs are proposed to recruit MIWI2 to the transcriptionally active TE loci by base pairing to nascent transcripts, however the downstream mechanisms and effector proteins utilized by MIWI2 in directing de novo TE methylation remain incompletely understood. Here, we show that MIWI2 associates with TEX15 in foetal gonocytes.

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Background: Hypoxia is pervasive in cancer and other diseases. Cells sense and adapt to hypoxia by activating hypoxia-inducible transcription factors (HIFs), but it is still an outstanding question why cell types differ in their transcriptional response to hypoxia.

Results: We report that HIFs fail to bind CpG dinucleotides that are methylated in their consensus binding sequence, both in in vitro biochemical binding assays and in vivo studies of differentially methylated isogenic cell lines.

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Article Synopsis
  • In mammals, there's a special part of the cells called the germline that helps pass traits to the next generation, but it needs to reset its DNA signals.
  • In male germ cells, a protein called MIWI2 works with special RNA bits called piRNAs to help silence potentially harmful parts of the DNA known as transposable elements.
  • Scientists discovered a new helper protein called SPOCD1 that is important for MIWI2 to do its job, and without it, male mice can’t have babies, but it doesn’t affect the production of piRNAs.
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Following publication of the original article [1], it was reported that the incorrect "Additional file 3" was published. The correct additional file is given below.

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Article Synopsis
  • Researchers found that mice lacking Piwil4 (Miwi2) and Dnmt3l had problems with sperm cell development because their genes weren’t properly reset.
  • This issue caused the mice to fail at silencing certain harmful elements in their DNA, leading to a loss of important sperm cells.
  • The study showed that instead of DNA damage, the problems came from changes in gene activity due to these unsilenced elements, which messed up how the sperm cells grew and developed.
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Background: Whole-genome bisulfite sequencing (WGBS) is becoming an increasingly accessible technique, used widely for both fundamental and disease-oriented research. Library preparation methods benefit from a variety of available kits, polymerases and bisulfite conversion protocols. Although some steps in the procedure, such as PCR amplification, are known to introduce biases, a systematic evaluation of biases in WGBS strategies is missing.

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Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs.

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Article Synopsis
  • In mice, a special pathway called PIWI-piRNA helps keep certain jumping genes, or transposons, from being active during the development of male reproductive cells.
  • The protein MILI helps manage this pathway by cutting up transposon RNA and making more piRNAs.
  • The study shows there’s another way to make piRNAs that helps MIWI2 work, even if MILI is not around.
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Primordial germ cell (PGC) development is characterized by global epigenetic remodeling, which resets genomic potential and establishes an epigenetic ground state. Here we recapitulate PGC specification in vitro from naive embryonic stem cells and characterize the early events of epigenetic reprogramming during the formation of the human and mouse germline. Following rapid de novo DNA methylation during priming to epiblast-like cells, methylation is globally erased in PGC-like cells.

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Mouse embryonic stem cells are dynamic and heterogeneous. For example, rare cells cycle through a state characterized by decondensed chromatin and expression of transcripts, including the Zscan4 cluster and MERVL endogenous retrovirus, which are usually restricted to preimplantation embryos. Here, we further characterize the dynamics and consequences of this transient cell state.

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Primordial germ cells (PGCs) are the embryonic precursors of the germ cell lineage that form sperm and egg cells. It is of great importance to preserve the germline from DNA damage and potentially from epimutations in order to ensure the survival of future generations. Recent research highlights the role of the protein arginine methyltransferase 5 (PRMT5) as an important player in DNA protection during germline development in the mouse (Kim , & Li , 2015).

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