Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore, Singapore.
YLL School of Medicine, National University of Singapore, 119228, Singapore, Singapore.
Nat Commun. 2021 Jan 4;12(1):43. doi: 10.1038/s41467-020-20282-1.
CCCTC binding factor (CTCF) is an important factor in the maintenance of chromatin-chromatin interactions, yet the mechanism regulating its binding to chromatin is unknown. We demonstrate that zinc finger protein 143 (ZNF143) is a key regulator for CTCF-bound promoter-enhancer loops. In the murine genome, a large percentage of CTCF and ZNF143 DNA binding motifs are distributed 37 bp apart in the convergent orientation. Furthermore, deletion of ZNF143 leads to loss of CTCF binding on promoter and enhancer regions associated with gene expression changes. CTCF-bound promoter-enhancer loops are also disrupted after excision of ZNF143. ZNF143-CTCF-bound promoter-enhancer loops regulate gene expression patterns essential for maintenance of murine hematopoietic stem and progenitor cell integrity. Our data suggest a common feature of gene regulation is that ZNF143 is a critical factor for CTCF-bound promoter-enhancer loops.
CCCTC 结合因子（CTCF）是维持染色质-染色质相互作用的重要因素，但调节其与染色质结合的机制尚不清楚。我们证明锌指蛋白 143（ZNF143）是 CTCF 结合启动子增强子环的关键调节因子。在小鼠基因组中，很大比例的 CTCF 和 ZNF143 DNA 结合基序以 37bp 的间隔呈会聚方向分布。此外，ZNF143 的缺失导致与基因表达变化相关的启动子和增强子区域的 CTCF 结合丧失。ZNF143 缺失后，CTCF 结合的启动子-增强子环也被破坏。ZNF143-CTCF 结合的启动子-增强子环调节维持小鼠造血干细胞和祖细胞完整性所必需的基因表达模式。我们的数据表明，基因调控的一个共同特征是 ZNF143 是 CTCF 结合启动子-增强子环的关键因素。
