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An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development.

Marlies E. Oomen,Diego Rodriguez-Terrones,M. Kurome,V. Zakhartchenko,Lorenza Mottes,K. Simmet,Camille Noll,Tsunetoshi Nakatani,Carlos Michel Mourra-Díaz,I. Aksoy,P. Savatier,Jonathan Göke,E. Wolf,Henrik Kaessmann,M. Torres‐Padilla

Published 2025 in Cell

ABSTRACT

Transcriptional activation of the embryonic genome (EGA) is a major developmental landmark enabling the embryo to become independent from maternal control. The magnitude and control of transcriptional reprogramming during this event across mammals remains poorly understood. Here, we developed Smart-seq+5' for high sensitivity, full-length transcript coverage and simultaneous capture of 5' transcript information from single cells and single embryos. Using Smart-seq+5', we profiled 34 developmental stages in 5 mammalian species and provide an extensive characterization of the transcriptional repertoire of early development before, during, and after EGA. We demonstrate widespread transposable element (TE)-driven transcription across species, including, remarkably, of DNA transposons. We identify 19,657 TE-driven genic transcripts, suggesting extensive TE co-option in early development over evolutionary timescales. TEs display similar expression dynamics across species and species-specific patterns, suggesting shared and divergent regulation. Our work provides a powerful resource for understanding transcriptional regulation of mammalian development.

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