| Description |
CCCTC-binding factor (CTCF) mutations cause intellectual impairment, developmental retardation, short stature, and mild cardiac malformations. However, the mechanism is still unknown. In this study, we constructed a mouse disease model harboring a clinically relevant CTCF missense mutation (R567W) and systematically analyzed the changes in transcriptome, CTCF binding and higher-order structure in several tissues by doing RNA-seq, snRNA-seq, ChIP-seq, BL-Hi-C experiments. Our data indicated that the homozygous CTCFR567W mutated mouse showed growth retardation, deficits in neural and cardiopulmonary development and lethality at birth. Mechanically, the CTCFR567W mutation globally weakened chromatin binding of CTCF, resulted in a rearrangement of the 3D genome structure and abnormal expression of cell-type specific genes. Together, We conclude that CTCF R567 plays a vital role in regulating normal development. |
