Research Paper Volume 14, Issue 12 pp 4959—4975

Time makes histone H3 modifications drift in mouse liver

Roman Hillje1, , Lucilla Luzi1, , Stefano Amatori2, , Giuseppe Persico1, , Francesca Casciaro4, , Martina Rusin1,2, , Mirco Fanelli2, , Piergiuseppe Pelicci1,3, , Marco Giorgio1,4, ,

  • 1 Department of Experimental Oncology, IRCCS - European Institute of Oncology, Milano 20139, Italy
  • 2 Department of Biomolecular Sciences, Molecular Pathology Lab, University of Urbino 'Carlo Bo', Fano 61032, Italy
  • 3 Department of Oncology and Hemato-Oncology, University of Milan, Milano 20122, Italy
  • 4 Department of Biomedical Sciences, University of Padua, Padova 35131, Italy

Received: November 1, 2021       Accepted: May 19, 2022       Published: June 10, 2022
How to Cite

Copyright: © 2022 Hillje et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


To detect the epigenetic drift of time passing, we determined the genome-wide distributions of mono- and tri-methylated lysine 4 and acetylated and tri-methylated lysine 27 of histone H3 in the livers of healthy 3, 6 and 12 months old C57BL/6 mice. The comparison of different age profiles of histone H3 marks revealed global redistribution of histone H3 modifications with time, in particular in intergenic regions and near transcription start sites, as well as altered correlation between the profiles of different histone modifications. Moreover, feeding mice with caloric restriction diet, a treatment known to retard aging, reduced the extent of changes occurring during the first year of life in these genomic regions.


ChIP-seq: chromatin immunoprecipitation sequencing; cLAD: constitutively lamina-associated domains; CR: caloric restriction; UMAP: Uniform Manifold Approximation and Projection; LINE: long interspersed nuclear elements; LTR: long terminal repeat retrotransposons; SD: standard diet; TSS: transcription start site.