Endogenous retroviral elements LTR8B and MER65 regulate the PSG9 locus that promotes trophoblast syncytialization: Insights into placental evolution and pre-eclampsia pathology

As retroelements (REs) are often lineage-specific and known to be co-opted for placental functioning, here we consider the RE binding of GATA3 and DLX5, these transcription factors being dysregulated in PE, and their downstream consequences.

Here we identify that the LTR8B cCREs facilitates the binding of transcription factors (e.g., GATA3, DLX5, TFAP2A/C), resulting in a diversified PSG gene expression pattern within a primate-specific genomic region that exhibits high intraspecies variability. The LTR8B/PSG9 regulatory element influences other PSG family members. PSG9, unique among PSGs, produces both secreted and membrane-anchored isoforms, MER65-int providing alternative polyA signals, enabling the evolution of secreted PSG variants through the truncation of the ancestral CEACAM protein’s transmembrane domain.