Distinct roles of two SEC scaffold proteins,AFF1 and AFF4,in regulating RNA polymerase Ⅱ transcription elongation  

作　　者：Zhuanzhuan Che Xiaoxu Liu Qian Dai Ke Fang Chenghao Guo Junjie Yue Haitong Fang Peng Xie Zhuojuan Luo Chengqi Lin 

机构地区：[1]The Key Laboratory of Developmental Genes and Human Disease,School of Life Science and Technology,Southeast University,Nanjing 210096,China [2]Co-innovation Center of Neuroregeneration,Nantong University,Nantong 226001,China [3]School of Biological Science and Medical Engineering,Southeast University,Nanjing 210096,China [4]Present address:School of Life Sciences,Anhui Medical University,Hefei 230032,China

出　　处：《Journal of Molecular Cell Biology》2023年第8期15-27,共13页分子细胞生物学报（英文版）

基　　金：supported by grants from the National Key R&D Program of China(2018YFA0800100 to C.L.,2018YFA0800103 to Z.L.);the National Natural Science Foundation of China(32030017 and 31970617 to C.L.,31970626 to Z.L.);Shenzhen Science and Technology Program(JCYJ20210324133602008 to C.L.,JCYJ20210324133601005 to Z.L.).

摘　　要：The super elongation complex(SEC)containing positive transcription elongation factor b plays a critical role in regulating transcription elongation.AFF1 and AFF4,two members of the AF4/FMR2 family,act as central scaffold proteins of SEC and are associated with various human diseases.However,their precise roles in transcriptional control remain unclear.Here,we investigate differences in the genomic distribution patterns of AFF1 and AFF4 around transcription start sites(TSSs).AFF1 mainly binds upstream of the TSS,while AFF4 is enriched downstream of the TSS.Notably,disruption of AFF4 results in slow elongation and early termination in a subset of AFF4-bound active genes,whereas AFF1 deletion leads to fast elongation and transcriptional readthrough in the same subset of genes.Additionally,AFF1 knockdown increases AFF4 levels at chromatin,and vice versa.In summary,these findings demonstrate that AFF1 and AFF4 function antagonistically to regulate RNA polymerase Ⅱ transcription.

关 键 词：super elongation complex AFF1 AFF4 transcription elongation early termination readthrough transcription 

分 类 号：Q51[生物学—生物化学]