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<p>Circadian oscillations of gene transcripts rely on a negative feedback loop executed by the activating BMAL1-CLOCK heterodimer and its negative regulators PER and CRY. Although circadian rhythms and CLOCK protein are mostly absent during embryogenesis, the lack of BMAL1 during prenatal development causes an early aging phenotype during adulthood, suggesting that BMAL1 performs an unknown non-circadian function during organism development that is fundamental for healthy adult life. Here, we show that BMAL1 interacts with TRIM28 and facilitates H3K9me3-mediated repression of transposable elements in naïve pluripotent cells, and that the loss of BMAL1 function induces a widespread transcriptional activation of MERVL elements, 3D genome reorganization and the acquisition of totipotency-associated molecular and cellular features. We propose that during embryogenesis, BMAL1 is redeployed as a transcriptional repressor of transposons in a CLOCK-independent way, and the activity of BMAL1-TRIM28 during prenatal life might protect mammalian organisms from premature aging during adulthood.</p>

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BMAL1-TRIM28 represses transposable elements independently of CLOCK in pluripotent cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月10日

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  • Amador Gallardo,
  • Efres Belmonte-Reche,
  • María Marti-Marimon,
  • Joan Domingo-Reinés,
  • Guillermo Peris,
  • Lourdes López-Onieva,
  • Iván Fernández-Rengel,
  • Jiajun Xie,
  • Pablo Tristán-Ramos,
  • Nicolas Bellora,
  • Antonio Sánchez-Pozo,
  • Antonio M. Estévez,
  • Sara R. Heras,
  • Marc A. Marti-Renom,
  • David Landeira

摘要

Circadian oscillations of gene transcripts rely on a negative feedback loop executed by the activating BMAL1-CLOCK heterodimer and its negative regulators PER and CRY. Although circadian rhythms and CLOCK protein are mostly absent during embryogenesis, the lack of BMAL1 during prenatal development causes an early aging phenotype during adulthood, suggesting that BMAL1 performs an unknown non-circadian function during organism development that is fundamental for healthy adult life. Here, we show that BMAL1 interacts with TRIM28 and facilitates H3K9me3-mediated repression of transposable elements in naïve pluripotent cells, and that the loss of BMAL1 function induces a widespread transcriptional activation of MERVL elements, 3D genome reorganization and the acquisition of totipotency-associated molecular and cellular features. We propose that during embryogenesis, BMAL1 is redeployed as a transcriptional repressor of transposons in a CLOCK-independent way, and the activity of BMAL1-TRIM28 during prenatal life might protect mammalian organisms from premature aging during adulthood.