tagHi-C Reveals 3D Chromatin Architecture Dynamics during Mouse Hematopoiesis
tagHi-C Reveals 3D Chromatin Architecture Dynamics during Mouse Hematopoiesis
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tagHi-C 揭示小鼠造血过程中的 3D 染色质结构动力学
DOI：
10.1016/j.celrep.2020.108206
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发表时间：
2020-09-29
期刊：
影响因子：
8.8
通讯作者：
Cheng, Hui
中科院分区：
文献类型：
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作者：
Zhang, Chao;Xu, Zihan;Cheng, Hui
造血分化过程中的时空染色质重组尚未得到全面表征，主要是因为目前的染色质构象捕获方法需要大量的起始细胞。在这里，我们介绍了一种基于低输入标记的Hi-C （tagHi-C）方法来捕获数百个细胞的染色质结构。利用tagHi-C，我们能够绘制出小鼠骨髓中10个初级造血干细胞、祖细胞和分化细胞群中染色质结构的时空动态。我们的研究结果表明，在造血细胞分化过程中，室动力学和Rabl结构发生了变化。我们确定基因体相关结构域（GADs）是高表达基因的一般结构。此外，我们通过空间染色质环扩展了受全基因组关联研究（GWAS）位点影响的基因的知识体系。我们的研究为研究少量细胞的三维（3D）基因组提供了tagHi-C方法，并绘制了骨髓造血细胞的全面三维染色质景观。
Spatiotemporal chromatin reorganization during hematopoietic differentiation has not been comprehensively characterized, mainly because of the large numbers of starting cells required for current chromatin conformation capture approaches. Here, we introduce a low-input tagmentation-based Hi-C (tagHi-C) method to capture the chromatin structures of hundreds of cells. Using tagHi-C, we are able to map the spatiotemporal dynamics of chromatin structure in ten primary hematopoietic stem, progenitor, and differentiated cell populations from mouse bone marrow. Our results reveal that changes in compartment dynamics and the Rabl configuration occur during hematopoietic cell differentiation. We identify gene-body-associating domains (GADs) as general structures for highly expressed genes. Moreover, we extend the body of knowledge regarding genes influenced by genome-wide association study (GWAS) loci through spatial chromatin looping. Our study provides the tagHi-C method for studying the three-dimensional (3D) genome of a small number of cells and maps the comprehensive 3D chromatin landscape of bone marrow hematopoietic cells.