机构：[1]Department of Pediatrics, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy,Chengdu 610041, China[2]Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children’sHospital Medical Center, Cincinnati, Ohio 45229, USA[3]Key Laboratory of Obstetrics, and Gynecologic and Pediatric Diseases and Birth Defects of Ministry ofEducation,West China Second Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China[4]Institute of Pharmacologyand Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China[5]Department of Veterinary Integrative Biosciences, TexasA&M University, College Station, Texas 77843, USA[6]Hubrecht Institute, Uppsalalaan 8, Utrecht 3584CT, The Netherlands[7]European Cancer Stem CellResearch Institute, Cardiff University, Cardiff CF244HQ, UK[8]Center for Translational Neuromedicine, University of Rochester Medical Center, 601 ElmwoodAvenue Rochester, New York 14642, USA[9]Key Laboratory of Birth Defects, Children’s Hospital of Fudan University, Shanghai 201102, China
Constitutive activation of Wnt/β-catenin inhibits oligodendrocyte myelination. Tcf7l2/Tcf4, a β-catenin transcriptional partner, is required for oligodendrocyte differentiation. How Tcf7l2 modifies β-catenin signalling and controls myelination remains elusive. Here we define a stage-specific Tcf7l2-regulated transcriptional circuitry in initiating and sustaining oligodendrocyte differentiation. Multistage genome occupancy analyses reveal that Tcf7l2 serially cooperates with distinct co-regulators to control oligodendrocyte lineage progression. At the differentiation onset, Tcf7l2 interacts with a transcriptional co-repressor Kaiso/Zbtb33 to block β-catenin signalling. During oligodendrocyte maturation, Tcf7l2 recruits and cooperates with Sox10 to promote myelination. In that context, Tcf7l2 directly activates cholesterol biosynthesis genes and cholesterol supplementation partially rescues oligodendrocyte differentiation defects in Tcf712 mutants. Together, we identify stage-specific co-regulators Kaiso and Sox10 that sequentially interact with Tcf7l2 to coordinate the switch at the transitions of differentiation initiation and maturation during oligodendrocyte development, and point to a previously unrecognized role of Tcf7l2 in control of cholesterol biosynthesis for CNS myelinogenesis.
基金：
This study was funded in part by grants
from the US National Institutes of Health (R01NS072427 and R01NS075243) and the
National Multiple Sclerosis Society (RG3978) to Q.R.L.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2023]版：
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小类|1 区综合性期刊
第一作者：
第一作者机构：[1]Department of Pediatrics, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy,Chengdu 610041, China[2]Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children’sHospital Medical Center, Cincinnati, Ohio 45229, USA
共同第一作者：
通讯作者：
通讯机构：[2]Division of Experimental Hematology and Cancer Biology, Department of Pediatrics, Brain Tumor Center, Cincinnati Children’sHospital Medical Center, Cincinnati, Ohio 45229, USA[3]Key Laboratory of Obstetrics, and Gynecologic and Pediatric Diseases and Birth Defects of Ministry ofEducation,West China Second Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China[9]Key Laboratory of Birth Defects, Children’s Hospital of Fudan University, Shanghai 201102, China
推荐引用方式(GB/T 7714)：
Zhao Chuntao,Deng Yaqi,Liu Lei,et al.Dual regulatory switch through interactions of Tcf7l2/Tcf4 with stage-specific partners propels oligodendroglial maturation.[J].Nature communications.2016,7:10883.doi:10.1038/ncomms10883.
APA：
Zhao Chuntao,Deng Yaqi,Liu Lei,Yu Kun,Zhang Liguo...&Lu Q Richard.(2016).Dual regulatory switch through interactions of Tcf7l2/Tcf4 with stage-specific partners propels oligodendroglial maturation..Nature communications,7,
MLA：
Zhao Chuntao,et al."Dual regulatory switch through interactions of Tcf7l2/Tcf4 with stage-specific partners propels oligodendroglial maturation.".Nature communications 7.(2016):10883
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