Grow et al. 2015 (PRJNA268222)

General Details

Title High-throughput sequencing of pluripotent cells
Organism
Number of Samples 8
Release Date 2014/11/21 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP050147
ENA SRP050147
GEO GSE63570
BioProject PRJNA268222

Publication

Title
Authors Grow EJ,Flynn RA,Chavez SL,Bayless NL,Wossidlo M,Wesche DJ,Martin L,Ware CB,Blish CA,Chang HY,Pera RA,Wysocka J
Journal Nature
Publication Date 2015 Jun 11
Abstract Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections, and comprise nearly 8% of the human genome. The most recently acquired human ERV is HERVK(HML-2), which repeatedly infected the primate lineage both before and after the divergence of the human and chimpanzee common ancestor. Unlike most other human ERVs, HERVK retained multiple copies of intact open reading frames encoding retroviral proteins. However, HERVK is transcriptionally silenced by the host, with the exception of in certain pathological contexts such as germ-cell tumours, melanoma or human immunodeficiency virus (HIV) infection. Here we demonstrate that DNA hypomethylation at long terminal repeat elements representing the most recent genomic integrations, together with transactivation by OCT4 (also known as POU5F1), synergistically facilitate HERVK expression. Consequently, HERVK is transcribed during normal human embryogenesis, beginning with embryonic genome activation at the eight-cell stage, continuing through the emergence of epiblast cells in preimplantation blastocysts, and ceasing during human embryonic stem cell derivation from blastocyst outgrowths. Remarkably, we detected HERVK viral-like particles and Gag proteins in human blastocysts, indicating that early human development proceeds in the presence of retroviral products. We further show that overexpression of one such product, the HERVK accessory protein Rec, in a pluripotent cell line is sufficient to increase IFITM1 levels on the cell surface and inhibit viral infection, suggesting at least one mechanism through which HERVK can induce viral restriction pathways in early embryonic cells. Moreover, Rec directly binds a subset of cellular RNAs and modulates their ribosome occupancy, indicating that complex interactions between retroviral proteins and host factors can fine-tune pathways of early human development.
PMC PMC4503379
PMID 25896322
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR1660328 PRJNA268222 Homo sapiens NCCIT cells, hECC Ribo-Seq Cycloheximide
SRR1660329 PRJNA268222 Homo sapiens NCCIT cells, hECC Ribo-Seq Cycloheximide
SRR1660330 PRJNA268222 Homo sapiens NCCIT cells, hECC Ribo-Seq Cycloheximide
SRR1660331 PRJNA268222 Homo sapiens naive hESC Ribo-Seq Cycloheximide
SRR1660332 PRJNA268222 Homo sapiens primed hESC Ribo-Seq Cycloheximide
SRR1660333 PRJNA268222 Homo sapiens NCCIT cells, hECC RNA-Seq Cycloheximide
SRR1660334 PRJNA268222 Homo sapiens NCCIT cells, hECC RNA-Seq Cycloheximide
SRR1660335 PRJNA268222 Homo sapiens NCCIT cells, hECC RNA-Seq Cycloheximide
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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