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 |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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