Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler.
Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler.
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DOI：
10.1083/jcb.201807108
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发表时间：
2018-11-05
期刊：
影响因子：
--
通讯作者：
Belmont AS
中科院分区：
文献类型：
--
作者：
Chen Y;Zhang Y;Wang Y;Zhang L;Brinkman EK;Adam SA;Goldman R;van Steensel B;Ma J;Belmont AS
陈等人。 TSA-Seq 是一种新的作图方法，可测量相对于空间上不同的核亚区室的细胞学距离。他们从人类细胞的新核组织图谱中识别出高基因密度的转录热点区域，这些区域靠近核斑点，富含高表达基因、看家基因和低转录暂停基因。虽然核区室化是三维基因组组织的基本特征，但不存在用于测量染色体与确定的核结构的距离的基因组方法。在这项研究中，我们描述了 TSA-Seq，这是一种新的作图方法，能够提供“细胞学标尺”，用于估计全基因组核斑点的平均染色体距离，并无需复杂的计算模型即可预测核区室之间的几个 Mbp 染色体轨迹。 K562 细胞的整体平均结果揭示了清晰的核纤层到斑点轴与基因组活性的显着空间梯度相关。该梯度代表多个空间分离的核域的卷积，包括两种类型的转录“热区”。转录热区突出到核内部最远并且定位非常接近核斑点，具有较高数量的总基因、最高表达的基因、管家基因、具有低转录暂停的基因和超级增强子。我们的结果证明了 TSA-Seq 用于核结构全基因组图谱的能力，并提出了转录和基因表达空间组织的新模型。
Chen et al. present TSA-Seq, a new mapping method that measures cytological distances relative to spatially distinct nuclear subcompartments. From novel nuclear organization maps of human cells, they identify transcription hot zones of high gene density that are near nuclear speckles and enriched in highly expressed genes, housekeeping genes, and genes with low transcriptional pausing. While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. In this study, we describe TSA-Seq, a new mapping method capable of providing a “cytological ruler” for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results in K562 cells reveal a clear nuclear lamina to speckle axis correlated with a striking spatial gradient in genome activity. This gradient represents a convolution of multiple spatially separated nuclear domains including two types of transcription “hot zones.” Transcription hot zones protruding furthest into the nuclear interior and positioning deterministically very close to nuclear speckles have higher numbers of total genes, the most highly expressed genes, housekeeping genes, genes with low transcriptional pausing, and super-enhancers. Our results demonstrate the capability of TSA-Seq for genome-wide mapping of nuclear structure and suggest a new model for spatial organization of transcription and gene expression.
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