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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Chen, S; Luperchio, TR; Wong, X; Doan, EB; Byrd, AT; Roy Choudhury, K; Reddy, KL; Krangel, MS

Published Date

  • November 13, 2018

Published In

Volume / Issue

  • 25 / 7

Start / End Page

  • 1729 - 1740.e6

PubMed ID

  • 30428344

Pubmed Central ID

  • PMC6287930

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2018.10.052


  • eng

Conference Location

  • United States