Marina-Zárate Ester, Rodríguez-Ronchel Ana, Gómez Manuel J, Sánchez-Cabo Fátima, Ramiro Almudena R
B Cell Biology Laboratory, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
Bioinformatics Unit, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
iScience. 2023 Feb 2;26(3):106106. doi: 10.1016/j.isci.2023.106106. eCollection 2023 Mar 17.
CTCF is a DNA-binding protein which plays critical roles in chromatin structure organization and transcriptional regulation; however, little is known about the functional determinants of different CTCF-binding sites (CBS). Using a conditional mouse model, we have identified one set of CBSs that are lost upon CTCF depletion (lost CBSs) and another set that persists (retained CBSs). Retained CBSs are more similar to the consensus CTCF-binding sequence and usually span tandem CTCF peaks. Lost CBSs are enriched at enhancers and promoters and associate with active chromatin marks and higher transcriptional activity. In contrast, retained CBSs are enriched at TAD and loop boundaries. Integration of ChIP-seq and RNA-seq data has revealed that retained CBSs are located at the boundaries between distinct chromatin states, acting as chromatin barriers. Our results provide evidence that transient, lost CBSs are involved in transcriptional regulation, whereas retained CBSs are critical for establishing higher-order chromatin architecture.
CTCF是一种DNA结合蛋白，在染色质结构组织和转录调控中发挥关键作用；然而，对于不同CTCF结合位点（CBS）的功能决定因素知之甚少。利用条件性小鼠模型，我们鉴定出一组在CTCF缺失时丢失的CBS（丢失的CBS）和另一组持续存在的CBS（保留的CBS）。保留的CBS与CTCF结合共有序列更相似，通常跨越串联CTCF峰。丢失的CBS在增强子和启动子处富集，并与活性染色质标记和更高的转录活性相关。相反，保留的CBS在拓扑相关结构域（TAD）和环边界处富集。ChIP-seq和RNA-seq数据的整合表明，保留的CBS位于不同染色质状态之间的边界，充当染色质屏障。我们的结果提供了证据，即短暂的、丢失的CBS参与转录调控，而保留的CBS对于建立高阶染色质结构至关重要。
