ANKRD11 binding to cohesin suggests a connection between KBG syndrome and Cornelia de Lange syndrome
成果类型：
Article
署名作者：
Liu, Haiyang; Li, Hao; Cai, Qixu; Zhang, Jie; Zhong, Hongxin; Hu, Gongcheng; Zhao, Shuaizhu; Lu, Yuli; Mao, Yudi; Lu, Youming; Yao, Hongjie; Zhang, Mingjie
署名单位：
Southern University of Science & Technology; Shenzhen Bay Laboratory; Huazhong University of Science & Technology; Huazhong University of Science & Technology; Huazhong University of Science & Technology; Xiamen University; State Key Laboratory of Respiratory Disease; Chinese Academy of Sciences; Guangzhou Institute of Biomedicine & Health, CAS; Guangzhou Laboratory; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-10605
DOI：
10.1073/pnas.2417346122
发表日期：
2025-01-28
关键词：
mutations
regulator
localization
ORGANIZATION
phenotype
genomes
ctcf
摘要：
Ankyrin Repeat Domain- containing Protein 11 (ANKRD11) is a causative gene for a highly confident autism spectrum disorder gene. Mutations of ANKRD11 lead to developmental abnormalities in multiple organs/tissues including the brain, craniofacial and skeletal bones, and tooth structures with unknown mechanism(s). Here, we find that ANKRD11, via a short peptide fragment in its N- terminal region, binds to the cohesin complex with a high affinity, implicating why ANKRD11 mutation can cause CdLS. The crystal structure of the ANKRD11 peptide in complex with cohesin, together with biochemical experiments, revealed that ANKRD11 competes with CCCTC- binding factor in binding to the cohesin complex. Importantly, a single point mutation in ANKRD11 and perturbed gene expressions in a mouse embryonic stem cell model. Mice carrying the ANKRD11 Y347A mutation display neural and craniofacial anomalies, which mirror ANKRD11 functions together with cohesin to regulate gene expression and also provides insights into the molecular mechanisms underpinning developmental disorders caused