AI Article Synopsis

  • Transposable elements (TEs), which make up nearly half of the human genome, play a crucial but poorly understood role in genomic innovation.
  • This study highlights how endogenous retroviruses (ERVs), a type of TE, regulate gene expression during the definitive endoderm stage in human embryonic stem cells.
  • Specifically, the ERV LTR6B has binding sites for important transcription factors and influences the expression of nearby developmental genes, suggesting that these ERVs are vital for species-specific development and gene regulation.

Article Abstract

Transposable elements (TEs) are the major sources of lineage-specific genomic innovation and comprise nearly half of the human genome, but most of their functions remain unclear. Here, we identify that a series of endogenous retroviruses (ERVs), a TE subclass, regulate the transcriptome at the definitive endoderm stage with in vitro differentiation model from human embryonic stem cell. Notably, these ERVs perform as enhancers containing binding sites for critical transcription factors for endoderm lineage specification. Genome-wide methylation analysis shows most of these ERVs are derepressed by TET1-mediated DNA demethylation. LTR6B, a representative definitive endoderm activating ERV, contains binding sites for FOXA2 and GATA4 and governs the primate-specific expression of its neighboring developmental genes such as ERBB4 in definitive endoderm. Together, our study proposes evidence that recently evolved ERVs represent potent de novo developmental regulatory elements, which, in turn, fine-tune species-specific transcriptomes during endoderm and embryonic development.

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Source
http://dx.doi.org/10.1016/j.celrep.2022.111791DOI Listing

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