Cell fate transition is a fascinating process involving complex dynamics of three-dimensional(3D)chromatin organization and phase separation,which play an essential role in cell fate decision by regulating gene expres...Cell fate transition is a fascinating process involving complex dynamics of three-dimensional(3D)chromatin organization and phase separation,which play an essential role in cell fate decision by regulating gene expression.Phase separation is increasingly being considered a driving force of chromatin folding.In this review,we have summarized the dynamic features of 3D chromatin and phase separation during physiological and pathological cell fate transitions and systematically analyzed recent evidence of phase separation facilitating the chromatin structure.In addition,we discuss current advances in understanding how phase separation contributes to physical and functional enhancerpromoter contacts.We highlight the functional roles of 3D chromatin organization and phase separation in cell fate transitions,and more explorations are required to study the regulatory relationship between 3D chromatin organization and phase separation.展开更多
Polycomb group(PcG)ring finger protein 6(PCGF6),though known as a member of the transcription-re-pressing complexes,PcG,also has activation function in regulating pluripotency gene expression.However,the mechanism und...Polycomb group(PcG)ring finger protein 6(PCGF6),though known as a member of the transcription-re-pressing complexes,PcG,also has activation function in regulating pluripotency gene expression.However,the mechanism underlying the activation function of PCGF6 is poorly understood.Here,we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as OCT4.In addition,PCGF6 was recruited to a subset of the super-enhancer(SE)regions upstream of cell cycle-associated genes by OCT4,and increased their expression.By combining with promoter capture Hi-C data,we found that PCGF6 activates cell cycle genes by regulating SE-promoter interactions via 3D chromatin.Our fin dings highlight a novel mechanism of PcG protein in regulating pluripotency,and provide a research basis for the therapeutic application of pluripotent stem cells.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.31970811,31771639 and 32170798)the Guangdong Regenerative Medicine and Health of Guangdong Laboratory Frontier Exploration Project(2018GZR110105007)+6 种基金the Guangdong Innovative and Entrepreneurial Research Team Program(2016ZT06S029)Guangdong Basic and Applied Basic Research Foundation(2011B1515120063)to J.D.the Fundamental Research Funds for the Central Universities of Jinan University(Natural Science)(2162004)China Postdoctoral Science Foundation(2021M701441)China Postdoctoral Special Grant Foundation(2022T150269)Guangdong Basic and Applied Basic Research Foundation(2021A1515)Guangzhou Basic and Applied Basic Research Foundation(202201010961)to L.F..
文摘Cell fate transition is a fascinating process involving complex dynamics of three-dimensional(3D)chromatin organization and phase separation,which play an essential role in cell fate decision by regulating gene expression.Phase separation is increasingly being considered a driving force of chromatin folding.In this review,we have summarized the dynamic features of 3D chromatin and phase separation during physiological and pathological cell fate transitions and systematically analyzed recent evidence of phase separation facilitating the chromatin structure.In addition,we discuss current advances in understanding how phase separation contributes to physical and functional enhancerpromoter contacts.We highlight the functional roles of 3D chromatin organization and phase separation in cell fate transitions,and more explorations are required to study the regulatory relationship between 3D chromatin organization and phase separation.
文摘Polycomb group(PcG)ring finger protein 6(PCGF6),though known as a member of the transcription-re-pressing complexes,PcG,also has activation function in regulating pluripotency gene expression.However,the mechanism underlying the activation function of PCGF6 is poorly understood.Here,we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as OCT4.In addition,PCGF6 was recruited to a subset of the super-enhancer(SE)regions upstream of cell cycle-associated genes by OCT4,and increased their expression.By combining with promoter capture Hi-C data,we found that PCGF6 activates cell cycle genes by regulating SE-promoter interactions via 3D chromatin.Our fin dings highlight a novel mechanism of PcG protein in regulating pluripotency,and provide a research basis for the therapeutic application of pluripotent stem cells.