A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus
| Autor: | Michael S. Krangel, Teresa Romeo Luperchio, Xianrong Wong, Aaron Byrd, Shiwei Chen, Europe B. Doan, Karen L. Reddy, Kingshuk Roy Choudhury |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Transcriptional Activation Transcription Genetic Receptors Antigen T-Cell alpha-beta Locus (genetics) Biology Models Biological General Biochemistry Genetics and Molecular Biology Article Cell Line Histones 03 medical and health sciences 0302 clinical medicine Animals Humans cardiovascular diseases Enhancer lcsh:QH301-705.5 Regulation of gene expression Recombination Genetic Nuclear Lamina Lysine V(D)J recombination Chromatin V(D)J Recombination Cell biology Mice Inbred C57BL 030104 developmental biology surgical procedures operative lcsh:Biology (General) CTCF Genetic Loci cardiovascular system Nuclear lamina 030217 neurology & neurosurgery Recombination circulatory and respiratory physiology |
| Zdroj: | Cell Reports, Vol 25, Iss 7, Pp 1729-1740.e6 (2018) |
| ISSN: | 2211-1247 |
| 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: | OpenAIRE |
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