{
  "cutoff": "2026-10-09",
  "note": "Selected publication milestones, not an exhaustive history or discovery priority claim.",
  "milestones": [
    {
      "pmid": "16878134",
      "year": "2006",
      "title": "Characterization of the Drosophila melanogaster genome at the nuclear lamina.",
      "doi": "10.1038/ng1852",
      "url": "https://pubmed.ncbi.nlm.nih.gov/16878134/",
      "interpretation": "2006Drosophila genome-wide lamina mapping establishes the descriptive low-expression association."
    },
    {
      "pmid": "18195101",
      "year": "2008",
      "title": "A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence.",
      "doi": "10.1083/jcb.200706060",
      "url": "https://pubmed.ncbi.nlm.nih.gov/18195101/",
      "interpretation": "2008synthetic peripheral transgene targeting retains inducible transcriptional competence."
    },
    {
      "pmid": "22116031",
      "year": "2011",
      "title": "Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells.",
      "doi": "10.1126/science.1211222",
      "url": "https://pubmed.ncbi.nlm.nih.gov/22116031/",
      "interpretation": "2011native lamin-null stem cells reveal tissue-building versus global-silencing distinctions."
    },
    {
      "pmid": "23226217",
      "year": "2012",
      "title": "Role of histone deacetylases in gene regulation at nuclear lamina.",
      "doi": "10.1371/journal.pone.0049692",
      "url": "https://pubmed.ncbi.nlm.nih.gov/23226217/",
      "interpretation": "2012local HDAC/lamin perturbations separate repression and position inDrosophila."
    },
    {
      "pmid": "23374351",
      "year": "2013",
      "title": "LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation.",
      "doi": "10.1016/j.cell.2013.01.009",
      "url": "https://pubmed.ncbi.nlm.nih.gov/23374351/",
      "interpretation": "2013LBRandA-type lamin tethers show sequential redundancy and opposite developmental effects."
    },
    {
      "pmid": "30201095",
      "year": "2018",
      "title": "Lamins Organize the Global Three-Dimensional Genome from the Nuclear Periphery.",
      "doi": "10.1016/j.molcel.2018.05.017",
      "url": "https://pubmed.ncbi.nlm.nih.gov/30201095/",
      "interpretation": "2018triple-lamin knockout/add-back tests topology while detached LAD genes resist uniform derepression."
    },
    {
      "pmid": "39322756",
      "year": "2024",
      "title": "Chromatin protein complexes involved in gene repression in lamina-associated domains.",
      "doi": "10.1038/s44318-024-00214-1",
      "url": "https://pubmed.ncbi.nlm.nih.gov/39322756/",
      "interpretation": "2024LADgenetic screens reveal local chromatin-regulator and promoter-context dependence."
    },
    {
      "pmid": "41735607",
      "year": "2026",
      "title": "LBR and LAP2 mediate heterochromatin tethering to the nuclear periphery to preserve genome homeostasis.",
      "doi": "10.1038/s41556-025-01822-7",
      "url": "https://pubmed.ncbi.nlm.nih.gov/41735607/",
      "interpretation": "2026LBR/LAP2deconvolution separates short detachment from chronic transcription/homeostasis effects."
    },
    {
      "pmid": "41909953",
      "year": "2026",
      "title": "B-type lamins maintain transcriptional homeostasis by spatially controlling chromatin-speckle proximity.",
      "doi": "10.1093/nar/gkag283",
      "url": "https://pubmed.ncbi.nlm.nih.gov/41909953/",
      "interpretation": "2026B-lamin knockout maps speckle-distance andRNAchanges with cell-viability confounding retained."
    }
  ],
  "gaps": [
    "Separate necessity of a silencing enzyme from necessity of its recruitment by lamin.",
    "Quantify native transcription after rapid detachment before chronic epigenetic/stress amplification.",
    "Dissect B-type versus A-type lamin functions and LBR/LAP2/LEM/PRR14 redundancy by cell state.",
    "Test whether speckle distance mediates RNA changes rather than being a correlated consequence of global disorganization.",
    "Separate mechanical and chromatin-tether rescue with endogenous matched alleles.",
    "Retain active LAD promoters and opposing differentiation effects in global prediction tests."
  ],
  "decisive_experiment": "Engineer an endogenous lamin allele that loses a specified silencer interaction while preserving filament mechanics, envelope integrity and redundant-tether localization. Compare it with a mechanical-defect allele and expression-matched rescue across predefined stem and differentiated states. Perform short-time-course native nascent RNA plus contact/speckle mapping, with cell-cycle, replication stress and viability controls. Re-tether the enzyme selectively at native affected loci to test whether repression is restored before downstream damage."
}