一个层粘连蛋白相关域边界控制核层粘连蛋白相互作用、转录和 TCRB 基因座的重组。
A Lamina-Associated Domain Border Governs Nuclear Lamina Interactions, Transcription, and Recombination of the Tcrb Locus.
机构信息
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Department of Biological Chemistry, Center for Epigenetics, Johns Hopkins University, Baltimore, MD 21205, USA.
出版信息
Cell Rep. 2018 Nov 13;25(7):1729-1740.e6. doi: 10.1016/j.celrep.2018.10.052.
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.
Tcrb 基因座 V(D)J 重组受核周定位调控。在这里，我们使用 DamID 以高分辨率描绘 Tcrb 基因座与核纤层的相互作用。我们鉴定了一个由几个 CTCF 结合元件组成的核纤层相关结构域 (LAD) 边界，该边界将活性非 LAD 与基因座的非活性 LAD 区域分隔开。LAD 边界缺失会导致组蛋白 H3 赖氨酸 27 乙酰化从活性重组中心依赖增强子的扩散到重组中心附近的 LAD 染色质。这与核纤层关联的破坏、与重组中心的染色质环增加以及重组中心附近基因片段的转录和重组增加有关。我们的结果表明，LAD 和 LAD 边界是 Tcrb 基因座基因调控的关键组成部分，并表明 LAD 边界通常可用于限制附近增强子的活性。
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