核细胞重塑剂对转录在cis调节元素的广泛影响
Benjamin J Patty1, Sarah J Hainer1,2
1Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA USA.
bioRxiv : the preprint server for biology
|April 25, 2024
概括
这项研究揭示了SNF2家族核细胞重塑剂如何调节小鼠胚胎干细胞中的基因表达. 许多重塑者通过改变染色质结构来控制编码和非编码RNA,并为不同类型的RNA提供不同的机制.
科学领域:
- * 分子生物学 * 分子生物学
- * 基因组学 是一个学科.
- * 基因调控 * 基因调控
背景情况:
- *核细胞重塑复合体对于建立细胞特异性基因表达模式至关重要.
- *Cis调节元件 (CREs),包括促进剂和增强剂,驱动mRNA和非编码RNA (ncRNA) 的转录.
- *两个关键的ncRNA是上游反意义RNA (uaRNA) 和增强RNA (eRNA).
研究的目的:
- * 探索控制小鼠胚胎干细胞中CRE相关转录 (mRNA,eRNA,uaRNA) 的核细胞重塑剂的调控网络.
- * 测试SNF2家族重塑剂通过核细胞结构协调调节转录组的假设.
- *确定未被研究的重塑剂在编码和非编码RNA调节中的新角色.
主要方法:
- * 在小鼠ES细胞中消耗SNF2家族重塑剂.
- * 暂时转录组测序 (TT-seq) 用于分析mRNA,eRNA和uaRNA水平的全球变化.
- * 机制研究,以调查特定重塑器的功能作用.
主要成果:
- * 在重建器耗尽后,成千上万的mRNA和CRE相关的ncRNA被错误调节.
- * 在未经研究的重塑器中发现了对转录调节的新贡献.
- *mRNA和eRNA转录是协调共同调节的.
- *来自共享促进者的mRNA和uaRNAs是独立调节的.
- * 改造器SRCAP和CHD8直接调节转录;像SMARCAL1这样的改造器通过基因组稳定性和整合器复合物定位间接调节它.
结论:
- *为CRE相关转录阐明了一个全面的基于重塑器的监管网络.
- *确定了至少两类SNF2家族重塑剂在转录调节中的作用.
- * 发现突出了重塑者在通过染色体调制维持编码和非编码转录组的协作作用.
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