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

Autor: Shiwei Chen, Teresa Romeo Luperchio, Xianrong Wong, Europe B. Doan, Aaron T. Byrd, Kingshuk Roy Choudhury, Karen L. Reddy, Michael S. Krangel
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Cell Reports, Vol 25, Iss 7, Pp 1729-1740.e6 (2018)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2018.10.052
Popis: Summary: 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. Keywords: T cell receptor β, Tcrb, V(D)J recombination, nuclear lamina, lamina-associated domain, LAD border, DamID, CTCF
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