{
  "id": 18034692,
  "title": "Genome-wide loss of chromatin accessibility coexists with selectively elevated RNA abundance in nutrient-starved U2OS cells",
  "url": "https://urgent.news/2026/11/03/genome-wide-loss-of-chromatin-accessibility-coexists-with-selectively",
  "topic": "science",
  "section": "Science",
  "published": "2026-11-03T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763108v1?rss=1"
  },
  "original_language": "en",
  "account": "A recent study in human U2OS osteosarcoma cells has revealed an intriguing phenomenon - a significant loss of chromatin accessibility across the genome during severe nutrient deprivation, accompanied by an unexpected elevation in RNA abundance for a select group of genes. This unexpected relationship between chromatin accessibility and RNA production challenges the conventional notion that chromatin accessibility directly governs transcript abundance, particularly under acute cellular stress conditions.\n\nThe researchers found that 18 hours of nutrient deprivation led to a genome-wide reduction in chromatin accessibility, affecting both promoter and enhancer regions. This reduction in accessibility was observed in housekeeping-gene promoters, as well as sites with CTCF motifs, pivotal elements in gene regulation. In contrast, RNA-seq analysis showed a more selective pattern of gene expression changes, with only a minority of expressed genes exhibiting differentially regulated steady-state RNA abundance. Remarkably, approximately 64% of these differentially expressed genes were found to have increased RNA levels, despite the overall loss of chromatin accessibility.\n\nThe correlation between chromatin accessibility and transcript abundance was modest at promoters (Pearson r = 0.25) and weak at enhancers (r = 0.10). Together, these factors accounted for only around 6% of the variance in transcript abundance changes. The relationship between the two seemed to depend on the specific gene, with genes experiencing smaller promoter losses being more likely to show increased RNA abundance compared to those with larger promoter losses. This relationship remained consistent in both actively growing and nutrient-deprived cells.\n\nPathway-level analysis further revealed that the observed changes in RNA abundance were linked to stress-adaptive programs, including extracellular matrix organization, lipid and cholesterol metabolism, small GTPase signalling, and developmental processes. Notably, genes involved in these adaptive programs exhibited increased RNA production despite reduced accessibility at their associated regulatory regions. This suggests that chromatin accessibility may act as a permissive rather than deterministic layer in gene regulation, allowing for transcriptional activation even when chromatin accessibility is reduced.\n\nThe findings of this study highlight the complex interplay between chromatin accessibility and RNA production during severe cellular stress. While chromatin accessibility serves as a vital layer of gene regulation, its ability to predict transcript abundance under such conditions is limited. Instead, the study supports the idea that chromatin accessibility can be a permissive factor, allowing transcription to occur even when its levels are low. This selective induction of adaptive programmes through altered RNA production further emphasizes the versatility of gene regulation in response to metabolic challenges. The researchers propose that compaction of chromatin, rather than accessible Tn5 accessibility, may be the underlying mechanism behind these observations, warranting further direct validation.",
  "summary": "Background Chromatin accessibility is widely used as a proxy for regulatory potential and is often interpreted together with RNA-seq to infer gene-regulatory responses. However, the quantitative relationship between chromatin accessibility and transcript abundance may become difficult to interpret, particularly under acute cellular stress. Metabolic challenges such as nutrient deprivation are…",
  "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."
}