转录组和染色质可访问性之间的分歧在从双潜在的原生细胞群体分化到红色母细胞和巨核细胞的过程中
Tejaswini Mishra1,2, Belinda M Giardine1,2, Christapher S Morrissey1,2
1Center for Computational Biology and Bioinformatics; Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA.
bioRxiv : the preprint server for biology
|July 9, 2025
概括
巨核细胞-红色素原始体 (MEPs) 启动了巨核细胞 (MEG) 和红色细胞 (ERY) 程序. 欧洲议会议员中的不一致的基因表达和染色质可访问性解释了它们在功能基因组学研究中的独特聚类.
科学领域:
- * 血液形成和细胞分化
- * 分子生物学和基因组学
- *表观遗传学和基因调节
背景情况:
- *细胞分化是由基因表达的变化驱动的,这与染色质的可访问性和修改有关.
- * 巨核细胞-红色素原体 (MEP) 产生红红细胞 (ERY) 和巨核细胞 (MEG).
- * 之前的研究发现了MEP与其他造血细胞的聚合方式的差异,基于RNA测序与染色质状态.
研究的目的:
- * 调查小鼠中的MEP,ERY和MEG的转录组和转录因子占用率.
- * 了解ERY和MEG血统承诺背后的监管机制.
- * 为了调和RNA-seq和染色体可访问性数据之间的观察到的不一致性.
主要方法:
- *深度测序多A+RNA以映射转录组.
- *对转录因子 (TF) 占用率的分析.
- *将差异性基因表达数据与染色体可访问性地图集成.
主要成果:
- *欧洲议会议员表达了MEG计划的很大一部分,同时保留了与骨髓相关的基因.
- * ERY细胞经历了广泛的基因诱导和泛血造和MEG基因的抑制.
- *明确的TF占用模式区分MEG和ERY程序,MEG基因显示持续的造血TF结合.
- * 某些ERY基因的候选cis调节元件 (cCREs) 在双能细胞中早期被激活.
- * 一些在MEP和MEG表达的基因在MEP中显示出染色质可访问性降低.
结论:
- * 基因表达和染色体可访问性动态揭示了ERY和MEG谱系承诺的不同的监管策略.
- * 早期的cCRE激活和MEP中不同的染色质可访问性有助于功能基因组学数据集群的不一致.
- * 欧洲议会议员内部的亚种群异质性可能解释了在各种基因组模式中观察到的不同聚类模式.
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