LINE-1 transcription in round spermatids is associated with accretion of 5-carboxylcytosine in their open reading frames

Commun Biol. 2021 Jun 7;4(1):691. doi: 10.1038/s42003-021-02217-8.


Chromatin of male and female gametes undergoes a number of reprogramming events during the transition from germ cell to embryonic developmental programs. Although the rearrangement of DNA methylation patterns occurring in the zygote has been extensively characterized, little is known about the dynamics of DNA modifications during spermatid maturation. Here, we demonstrate that the dynamics of 5-carboxylcytosine (5caC) correlate with active transcription of LINE-1 retroelements during murine spermiogenesis. We show that the open reading frames of active and evolutionary young LINE-1s are 5caC-enriched in round spermatids and 5caC is eliminated from LINE-1s and spermiogenesis-specific genes during spermatid maturation, being simultaneously retained at promoters and introns of developmental genes. Our results reveal an association of 5caC with activity of LINE-1 retrotransposons suggesting a potential direct role for this DNA modification in fine regulation of their transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytosine / analogs & derivatives*
  • Cytosine / metabolism
  • Long Interspersed Nucleotide Elements*
  • Male
  • Mice
  • Open Reading Frames*
  • Spermatids / cytology
  • Spermatids / metabolism*
  • Spermatogenesis
  • Transcription, Genetic


  • 5-carboxylcytosine
  • Cytosine