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

Shiwei Chen, Teresa Romeo Luperchio, Xianrong Wong, Europe B. Doan, Aaron T. Byrd, Kingshuk Roy Choudhury, Karen L Reddy, Michael S. Krangel

Research output: Contribution to journalArticle

Abstract

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. Chen et al. identify a Tcrb locus lamina-associated domain border that constrains the activity of the Tcrb enhancer. Deletion of the border causes enhancer-dependent loss of nuclear lamina association, spreading of H3K27 acetylation, and elevated transcription and VDJ recombination of gene segments in affected chromatin.

Original languageEnglish (US)
JournalCell Reports
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Nuclear Lamina
Transcription
Genetic Recombination
Chromatin
Acetylation
V(D)J Recombination
Genes
Association reactions
Gene expression
Histones
Lysine

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chen, S., Luperchio, T. R., Wong, X., Doan, E. B., Byrd, A. T., Roy Choudhury, K., ... Krangel, M. S. (Accepted/In press). A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus. Cell Reports. https://doi.org/10.1016/j.celrep.2018.10.052

A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus. / Chen, Shiwei; Luperchio, Teresa Romeo; Wong, Xianrong; Doan, Europe B.; Byrd, Aaron T.; Roy Choudhury, Kingshuk; Reddy, Karen L; Krangel, Michael S.

In: Cell Reports, 01.01.2018.

Research output: Contribution to journalArticle

Chen, Shiwei ; Luperchio, Teresa Romeo ; Wong, Xianrong ; Doan, Europe B. ; Byrd, Aaron T. ; Roy Choudhury, Kingshuk ; Reddy, Karen L ; Krangel, Michael S. / A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus. In: Cell Reports. 2018.
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abstract = "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. Chen et al. identify a Tcrb locus lamina-associated domain border that constrains the activity of the Tcrb enhancer. Deletion of the border causes enhancer-dependent loss of nuclear lamina association, spreading of H3K27 acetylation, and elevated transcription and VDJ recombination of gene segments in affected chromatin.",
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