Endogenous retrovirus control of calbindin is essential for human early embryogenesis.

Authors

Judith Pape, Afshan McCarthy, Eduardo Serna-Morales, Borzo Gharibi, Tobias Plowman, Elias Copin, Rachael Thompson, Laura Doglio, Ruta Meleckyte-Martinez, Lyn Healy, Sara Tamagno, Alberto Elosegui-Artola, Silvia D M Santos, Kathy K Niakan, George Kassiotis

Published in

Science advances. Volume 12. Issue 41. Pages eaee4523. Oct 09, 2026. Epub Oct 07, 2026.

Abstract

The cis-regulatory potential of human endogenous retroviruses (HERVs) that have accumulated in our genome affects diverse host processes, including embryonic development and malignancy, where HERV epigenetic control is reduced. Non-small cell lung cancer optimal growth requires cancer cell-intrinsic expression of the calcium-binding protein calbindin under the control of a HERVH integrant on chromosome 8q21.3. Chimeric transcription of HERVH and CALB1, encoding calbindin, is also observed in human embryonic stem cells (ESCs), but its significance remained uncertain. Here, we show that HERVH integration on 8q21.3 during Homininae evolution coincides with acquisition of expression of CALB1 in preimplantation embryos. We further show that CALB1 expression is critical for human ESC growth and the prevention of cellular senescence and for the formation of ESC-derived preimplantation blastoids and postgastrulation amnioids. Thus, the co-option of HERVH 8q21.3 cis-regulatory activity in lung cancer may echo its essential requirement for human embryo development.

PMID:
42842653
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

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