Mapping the micro-proteome of the nuclear lamina and lamina-associated domains

Life Sci Alliance. 2021 Mar 23;4(5):e202000774. doi: 10.26508/lsa.202000774. Print 2021 May.


The nuclear lamina is a proteinaceous network of filaments that provide both structural and gene regulatory functions by tethering proteins and large domains of DNA, the so-called lamina-associated domains (LADs), to the periphery of the nucleus. LADs are a large fraction of the mammalian genome that are repressed, in part, by their association to the nuclear periphery. The genesis and maintenance of LADs is poorly understood as are the proteins that participate in these functions. In an effort to identify proteins that reside at the nuclear periphery and potentially interact with LADs, we have taken a two-pronged approach. First, we have undertaken an interactome analysis of the inner nuclear membrane bound LAP2β to further characterize the nuclear lamina proteome. To accomplish this, we have leveraged the BioID system, which previously has been successfully used to characterize the nuclear lamina proteome. Second, we have established a system to identify proteins that bind to LADs by developing a chromatin-directed BioID system. We combined the BioID system with the m6A-tracer system which binds to LADs in live cells to identify both LAD proximal and nuclear lamina proteins. In combining these datasets, we have further characterized the protein network at the nuclear lamina, identified putative LAD proximal proteins and found several proteins that appear to interface with both micro-proteomes. Importantly, several proteins essential for LAD function, including heterochromatin regulating proteins related to H3K9 methylation, were identified in this study.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Chromatin / metabolism
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology
  • Genome
  • Heterochromatin / metabolism
  • Humans
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology
  • Mice
  • NIH 3T3 Cells
  • Nuclear Lamina / genetics
  • Nuclear Lamina / metabolism*
  • Nuclear Lamina / pathology
  • Nuclear Proteins / genetics
  • Protein Binding / physiology
  • Protein Domains / physiology
  • Proteome / genetics
  • Proteome / metabolism*
  • Proteomics / methods


  • Chromatin
  • DNA-Binding Proteins
  • Heterochromatin
  • Membrane Proteins
  • Nuclear Proteins
  • Proteome
  • lamina-associated polypeptide 2
  • DNA

Associated data

  • GENBANK/GO:0034399
  • GENBANK/GO:0005652
  • GENBANK/GO:0016363