{
  "id": 10719119,
  "title": "Ctcf deficiency in myofibers induces pathological genome reprogramming toward the spontaneous development of myopathy",
  "url": "https://urgent.news/2026/09/29/ctcf-deficiency-in-myofibers-induces-pathological-genome",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-29T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.28.754564v1?rss=1"
  },
  "original_language": "en",
  "account": "In a groundbreaking study, researchers have uncovered the role of the Ctcf gene in maintaining the identity and function of skeletal myofibers throughout a person's life. By generating mice with a deficiency in Ctcf specifically in their muscle fibers, scientists observed that these mice did not exhibit any muscular abnormalities at birth. However, as the mice aged, they spontaneously developed severe myopathy, or muscle disease.\n\nThrough a comprehensive analysis of snRNAseq, ATACseq, and promoter-capture Hi-C, the team identified both shared and fiber-type specific changes in gene expression, chromatin accessibility, and promoter-based interactions in myonuclei of Ctcf-deficient mice. At the initial stages of myopathy development, decreased chromatin accessibility at promoters and modifications in their connectivity with distal elements were observed. These alterations were directly linked to the downregulation of genes involved in myofiber contraction, anabolism, metabolism, adhesion, and neuromuscular transmission.\n\nAs the myopathy progressed, the researchers found that Ctcf deficiency led to global reconfiguration of chromatin structure and connectivity. This resulted in the upregulation of genes that triggered persistent activation of ER stress/UPR and catabolism. This shift in gene expression, partly due to the indirect effects of Ctcf deficiency, played a significant role in the progression of the disease.\n\nInterestingly, the study revealed that type-IIB myonuclei exhibited distinct alterations in gene expression, leading to a loss of fiber-type identity and the ectopic expression of inflammatory genes. This finding highlights the importance of Ctcf in preserving fiber-type identity and transcriptional adaptation in myofibers.\n\nThe researchers emphasize that Ctcf plays a crucial role in maintaining the 3D genome integrity in skeletal myofibers, which is essential for proper muscle function and homeostasis. Moreover, their findings suggest an unexpected link between Ctcf deficiency in myofibers and the susceptibility to develop myopathies. It appears that while Ctcf is dispensable for developmental myogenesis, its absence increases the vulnerability of myofibers to develop myopathic syndromes later in life.",
  "summary": "How perennial, postmitotic multinucleated tissues, such as skeletal myofibers, maintain their identity and transcriptional adaptation to homeostatic perturbations through adult life is an outstanding question. To address this issue, we investigated the consequences of loss of 3D-genome architecture in skeletal muscles by generating myofiber-specific Ctcf-deficient (CtcfmKO) mice. CtcfmKO mice did…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}