Systematic analysis identifies a connection between spatial and genomic variations of chromatin states.

Cell systems Pub Date : 2024-11-20 Epub Date: 2024-11-13 DOI:10.1016/j.cels.2024.10.006
Xuan Cao, Terry Ma, Rong Fan, Guo-Cheng Yuan
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Abstract

Chromatin states play important roles in the maintenance of cell identities, yet their spatial patterns remain poorly characterized at the organism scale. We developed a systematic approach to analyzing spatial epigenomic data and then applied it to a recently published spatial-CUT&Tag dataset that was obtained from a mouse embryo. We identified a set of spatial genes whose H3K4me3 patterns delineate tissue boundaries. These genes are enriched with tissue-specific transcription factors, and their corresponding genomic loci are marked by broad H3K4me3 domains. Integrative analysis with H3K27me3 profiles showed coordinated spatial transitions across tissue boundaries, which is marked by the continuous shortening of H3K4me3 domains and expansion of H3K27me3 domains. Motif-based analysis identified transcription factors whose activities change significantly during such transitions. Taken together, our systematic analyses reveal a strong connection between the genomic and spatial variations of chromatin states. A record of this paper's transparent peer review process is included in the supplemental information.

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系统分析确定了染色质状态的空间变化与基因组变化之间的联系。
染色质状态在维持细胞特性方面发挥着重要作用,但它们的空间模式在生物体尺度上的表征还很不完善。我们开发了一种分析空间表观基因组数据的系统方法,然后将其应用于最近发表的空间-CUT&Tag 数据集,该数据集来自小鼠胚胎。我们发现了一组空间基因,其 H3K4me3 模式划定了组织边界。这些基因富含组织特异性转录因子,其相应的基因组位点被宽泛的 H3K4me3 域标记。与 H3K27me3 图谱的整合分析表明,跨组织边界的协调空间转换以 H3K4me3 域的持续缩短和 H3K27me3 域的扩展为标志。基于动因的分析确定了在这种转变过程中其活性发生显著变化的转录因子。总之,我们的系统分析揭示了染色质状态的基因组和空间变化之间的紧密联系。本文的同行评审过程透明,相关记录见补充信息。
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