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Distinct roles of two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA polymerase II transcription elongation 
Zhuanzhuan Che1,† , Xiaoxu Liu1,2,† , Qian Dai1,4,† , Ke Fang1 , Chenghao Guo1 , Junjie Yue1 , Haitong Fang1 , Peng Xie3 , Zhuojuan Luo1,2,* , Chengqi Lin1,2,*
1The Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210096, China
2Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
3School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
4Present address: School of Life Sciences, Anhui Medical University, Hefei 230032, China
†These authors contributed equally to this work.
*Correspondence to:Chengqi Lin , Email:cqlin@seu.edu.cn Zhuojuan Luo , Email:zjluo@seu.edu.cn
J Mol Cell Biol, Volume 15, Issue 8, August 2023, mjad049,  https://doi.org/10.1093/jmcb/mjad049
Keyword: super elongation complex, AFF1, AFF4, transcription elongation, early termination, readthrough transcription

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.


Volume 15, Issue 8
August 2023