Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Cell Syst. 2024 Nov 20;15(11):1092-1102.e2. doi: 10.1016/j.cels.2024.10.006. Epub 2024 Nov 13.
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.
染色质状态在维持细胞身份方面起着重要作用，但它们在生物体尺度上的空间模式仍未得到很好的描述。我们开发了一种系统的方法来分析空间表观基因组数据，然后将其应用于最近发表的来自小鼠胚胎的空间 CUT&Tag 数据集。我们确定了一组空间基因，其 H3K4me3 模式描绘了组织边界。这些基因富含组织特异性转录因子，其相应的基因组位点由广泛的 H3K4me3 结构域标记。与 H3K27me3 图谱的综合分析显示，组织边界处存在协调的空间转变，其特征是 H3K4me3 结构域的连续缩短和 H3K27me3 结构域的扩展。基于基序的分析确定了在这些转变过程中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。本论文的透明同行评审过程记录包含在补充信息中。
