THE1B may have no role in human pregnancy due to ZNF430-mediated silencing

THE1-family retrovirus invaded the primate genome more than 40 million years ago. Dunn-Fletcher et al. reported one THE1B element upstream of CRH gene alters gestation length by upregulating corticotropin-releasing hormone expression in transgenic mice and concluded it has the same role in human as well. However, no promoter or enhancer mark has been detected around this CRH-proximal element in any human tissue or cell, so probably some anti-viral factor exists in primates to prevents it from wreaking havoc. Here I report two paralogous zinc finger genes, ZNF430 and ZNF100, that emerged during the simian lineage to specifically silence THE1B and THE1A, respectively. Contact residue changes in one finger confers each ZNF the unique ability to preferentially repress one THE1 sub-family over the other. The reported THE1B element contains an intact ZNF430 binding site, thus under the repression of ZNF430 in most tissues including placenta, it is questionable whether or not this retrovirus has any role in human pregnancy. Overall, this analysis highlights the need to study human retroviruses’ functions in suitable model system. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13100-023-00294-6.