小柯机器人

研究绘制活化B细胞的顺式调控组
2019-12-25 11:22

美国辛辛那提儿童医院医疗中心Harinder Singh团队通过偶联结构和功能基因组图谱,描绘了活化B细胞的顺式调控组。相关论文2019年12月23日在线发表在《自然—免疫学》上。

研究人员表示,免疫细胞特异性基因组状态中的顺式调控组已被基于结构的染色质分析进行了广泛研究。

通过将此类方法与高通量增强子筛选结合(自转录活性调节区测序,STARR–seq),研究人员获得了脂多糖激活的B细胞的功能性顺式调控组。与缺乏增强子活性的可及性染色质区域相反,功能增强子富含增强子RNA(eRNA),并在体内优先与B细胞谱系决定转录因子相互作用。有趣的是,这些转录因子的优先组合型结合与它们位点的差异富集无关。取而代之的是,活性增强子通过主成分分析(PCA)从所有可及区域得以解析。高分辨率染色体构象捕获(Hi-C)分析揭示了多重激活的启动子-启动子构型,其包含许多参与不同分子途径控制的多增强子基因和多基因增强子。通路特异性增强子的基序分析为涵盖B细胞活化、循环和分化的生物过程提供了多种转录因子编码的目录。

附:英文原文

Title: Charting the cis-regulome of activated B cells by coupling structural and functional genomics

Author: Virendra K. Chaudhri, Krista Dienger-Stambaugh, Zhiguo Wu, Mahesh Shrestha, Harinder Singh

Issue&Volume: 2019-12-23

Abstract: Cis-regulomes underlying immune-cell-specific genomic states have been extensively analyzed by structure-based chromatin profiling. By coupling such approaches with a high-throughput enhancer screen (self-transcribing active regulatory region sequencing (STARR–seq)), we assembled a functional cis-regulome for lipopolysaccharide-activated B cells. Functional enhancers, in contrast with accessible chromatin regions that lack enhancer activity, were enriched for enhancer RNAs (eRNAs) and preferentially interacted in vivo with B cell lineage-determining transcription factors. Interestingly, preferential combinatorial binding by these transcription factors was not associated with differential enrichment of their sites. Instead, active enhancers were resolved by principal component analysis (PCA) from all accessible regions by co-varying transcription factor motif scores involving a distinct set of signaling-induced transcription factors. High-resolution chromosome conformation capture (Hi-C) analysis revealed multiplex, activated enhancer–promoter configurations encompassing numerous multi-enhancer genes and multi-genic enhancers engaged in the control of divergent molecular pathways. Motif analysis of pathway-specific enhancers provides a catalog of diverse transcription factor codes for biological processes encompassing B cell activation, cycling and differentiation.

DOI: 10.1038/s41590-019-0565-0

Source: https://www.nature.com/articles/s41590-019-0565-0

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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