Zebrafish ELL-associated factors Eaf1/2 modulate erythropoiesis via regulating gata1a expression and WNT signaling to facilitate hypoxia tolerance  

作　　者：WenYe Liu ShuHui Lin LingYa Li ZhiPeng Tai Jing-Xia Liu 

机构地区：[1]College of Fisheries,Key Laboratory of Freshwater Animal Breeding,Ministry of Agriculture,Huazhong Agricultural University,430070 Wuhan,China

出　　处：《Cell Regeneration》2023年第1期295-312,共18页细胞再生（英文）

基　　金：supported by the Nation Natural Science Foundation of China(Program No.32070807);by the National Key R&D Program of China(2018YFD0900101);by the project 2020SKLBC-KF06 of State Key Laboratory of Biocontrol.

摘　　要：EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto actively regulate a variety of biological processes,including leukemia and embryogenesis,but whether and how EAF1/2 function in hematopoietic system related hypoxia tolerance during embryogenesis remains unclear.Here,we unveiled that deletion of EAF1/2(eaf1^(-/-)and eaf2^(-/-))caused reduction in hypoxia tolerance in zebrafish,leading to reduced erythropoiesis during hematopoietic processes.Meanwhile,eaf1^(-/-)and eaf2^(-/-)mutants showed significant reduc-tion in the expression of key transcriptional regulators scl,lmo2,and gata1a in erythropoiesis at both 24 h post fertilization(hpf)and 72 hpf,with gata1a downregulated while scl and lmo2 upregulated at 14 hpf.Mechanistically,eaf1^(-/-)and eaf2^(-/-)mutants exhibited significant changes in the expression of epigenetic modified histones,with a significant increase in the binding enrichment of modified histone H3K27me3 in gata1a promoter rather than scl and lmo2 promoters.Additionally,eaf1^(-/-)and eaf2^(-/-)mutants exhibited a dynamic expression of canonical WNT/β-catenin signaling during erythropoiesis,with significant reduction in p-β-Catenin level and in the binding enrichment of both scl and lmo2 promoters with the WNT transcriptional factor TCF4 at 24 hpf.These findings demonstrate an important role of Eaf1/2 in erythropoiesis in zebrafish and may have shed some light on regeneration medicine for anemia and related diseases and on molecular basis for fish economic or productive traits,such as growth,disease resistance,hypoxia tolerance,and so on.

关 键 词：EAF1/2 gata1a/scl/lmo2 ERYTHROPOIESIS H3K27me3 WNT/β-Catenin signaling TCF4 

分 类 号：R33[医药卫生—人体生理学]