A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus

Cell Rep. 2018 Nov 13;25(7):1729-1740.e6. doi: 10.1016/j.celrep.2018.10.052.


Tcrb locus V(D)J recombination is regulated by positioning at the nuclear periphery. Here, we used DamID to profile Tcrb locus interactions with the nuclear lamina at high resolution. We identified a lamina-associated domain (LAD) border composed of several CTCF-binding elements that segregates active non-LAD from inactive LAD regions of the locus. Deletion of the LAD border causes an enhancer-dependent spread of histone H3 lysine 27 acetylation from the active recombination center into recombination center-proximal LAD chromatin. This is associated with a disruption to nuclear lamina association, increased chromatin looping to the recombination center, and increased transcription and recombination of recombination center-proximal gene segments. Our results show that a LAD and LAD border are critical components of Tcrb locus gene regulation and suggest that LAD borders may generally function to constrain the activity of nearby enhancers.

Keywords: CTCF; DamID; LAD border; T cell receptor β; Tcrb; V(D)J recombination; lamina-associated domain; nuclear lamina.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Chromatin / metabolism
  • Genetic Loci*
  • Histones / metabolism
  • Humans
  • Lysine / metabolism
  • Mice, Inbred C57BL
  • Models, Biological
  • Nuclear Lamina / metabolism*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Recombination, Genetic / genetics*
  • Transcription, Genetic*
  • Transcriptional Activation / genetics
  • V(D)J Recombination / genetics


  • Chromatin
  • Histones
  • Receptors, Antigen, T-Cell, alpha-beta
  • Lysine