Researchers at the University of Granada, in collaboration with national and international scientific groups, have shown that the BMAL1 protein, known for regulating circadian rhythms, acts as a guardian of the genome in embryos, opening up new perspectives for understanding aging and the origin of multiple human diseases.
A multidisciplinary team of scientists from the UGR, belonging to the Department of Biochemistry and Molecular Biology II and the research group 鈥楨pigenetic memory in disease鈥, has identified an unknown function of the BMAL1 protein during embryonic development in mice.
Traditionally, BMAL1 has been studied as part of the 鈥榗ircadian clock鈥, the molecular machinery that regulates the daily rhythms of the human organism. However, this study reveals that, in the early stages of life, this protein acts independently of the biological clock, associating with another protein, TRIM28, to keep retrotransposons, fragments of DNA capable of 鈥榡umping鈥 within the genome and altering its function, inactive.
The results show that the absence of BMAL1 in mouse embryonic stem cells causes the massive activation of these mobile elements, generating changes in the 3D organization of the genome and alterations in the functionality of the cells that form the embryo. This genomic disruption is probably linked to the premature aging previously described in BMAL1-deficient mice.
Amador Gallardo, first author of the paper, explains: 鈥淥ur results support the idea that BMAL1 plays an essential protective role during embryonic development, independent of its role in the circadian clock.鈥
David Landeira, principal investigator of the group and corresponding author of the paper, explains: 鈥淲e believe that this mechanism may underlie the accelerated aging observed in mutant animal models for the circadian clock and, potentially, the onset of age-related human diseases.鈥
Biomedical relevance
The finding opens up a new paradigm in biomedicine: proteins classically associated with the circadian clock may have alternative functions during development that are crucial for maintaining genome stability and cellular identity.
鈥淭hese discoveries reinforce the emerging idea that aging begins in the early stages of embryonic development, and not only in adulthood, as previously thought,鈥 the scientists note.
Publication and collaborations
The research, which has been published in the prestigious journal Nature Communications, was led by the 鈥楨pigenetic Memory in Disease鈥 group of the Department of Biochemistry and Molecular Biology II at the University of Granada, affiliated with the GENYO and ibs Center for Genomics and Oncological Research. GRANADA, in collaboration with other Spanish and international centers such as CRG (Barcelona), CSIC-IPBLN (Granada), and CONICET-INTECNUS (Argentina).
Bibliographic reference:
Gallardo, A., Belmonte-Reche, E., Marti-Marimon, M., Domingo-Rein茅s, J., Peris, G., L贸pez-Onieva, L., Fern谩ndez-Rengel, I., Xie, J., Trist谩n-Ramos, P., Bellora, N., S谩nchez-Pozo, A., Est茅vez, A.M., Heras, S.R., Marti-Renom, M.A. & Landeira, D. (2025). 鈥淏MAL1-TRIM28 represses transposable elements independently of CLOCK in pluripotent cells鈥. Nature Communications. DOI: https://doi.org/10.1038/s41467-025-63778-4
Contact:
David Landeira
UGR 鈥楨pigenetic memory in disease鈥 group
Centre for Genomics and Oncological Research (GENYO)
Phone: +34 958 715 500 (ext. 136)
贰尘补颈濒:听@email
奥别产蝉颈迟别:听
This text has been generated using machine translation and has not been revised, The UGR does not guarantee the accuracy of the translation and accepts no liability for possible errors.
