ArticleThe EMBO journal2020
Heterochromatin loosening by the Oct4 linker region facilitates Klf4 binding and iPSC reprogramming.
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Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33 citing papers in PubMed, 44 citations in OpenAlex.
- Single-Short Partial Reprogramming of the Endothelial Cells Decreases Blood Pressure via Attenuation of EndMT in Hypertensive Mice.Circulation research · 2025Article
- Hypo-osmolarity promotes naive pluripotency by reshaping cytoskeleton and increasing chromatin accessibility.Journal of advanced research · 2025Article
- Alternative splicing of KLF4 in myeloid cells: implications for cellular plasticity and trained immunity in cancer and inflammatory disease.Frontiers in immunology · 2025Review
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- BRG1 improves reprogramming efficiency by enhancing glycolytic metabolism.Cellular and molecular life sciences : CMLS · 2024Article
- Deciphering Mechanisms of Adipocyte Differentiation in Abdominal Fat of Broilers.Journal of agricultural and food chemistry · 2024Article
- Dedifferentiation-like reprogramming of degenerative nucleus pulposus cells into notochordal-like cells by defined factors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Article
- Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader.Nucleic acids research · 2024Article
- Pioneer factors: roles and their regulation in development.Trends in genetics : TIG · 2024Review
- Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming.Nature aging · 2024Review
- Diverse heterochromatin states restricting cell identity and reprogramming.Trends in biochemical sciences · 2023Review
- MUC1-C is necessary for SHP2 activation and BRAF inhibitor resistance in BRAF(V600E) mutant colorectal cancer.Cancer letters · 2023Article
- KLF4 transcription factor in tumorigenesis.Cell death discovery · 2023Review
- Nuclear localization of mitochondrial TCA cycle enzymes modulates pluripotency via histone acetylation.Nature communications · 2022Article
- TGFB2-AS1 inhibits triple-negative breast cancer progression via interaction with SMARCA4 and regulating its targetsProceedings of the National Academy of Sciences of the United States of America · 2022Article
- MiR-106b-5p Regulates the Reprogramming of Spermatogonial Stem Cells into iPSC (Induced Pluripotent Stem Cell)-Like CellsIranian biomedical journal · 2022Article
- Oct4 differentially regulates chromatin opening and enhancer transcription in pluripotent stem cells.eLife · 2022Article
- MAP2K6 remodels chromatin and facilitates reprogramming by activating Gatad2b-phosphorylation dependent heterochromatin loosening.Cell death and differentiation · 2022Article
- Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma.The Journal of clinical investigation · 2022Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Keshi ChenCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0003-0402-4555
Qi LongCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-7003-0104
Guangsuo XingCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Tianyu WangCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0003-4169-8268
Yi WuCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Linpeng LiCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Juntao QiCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Yanshuang ZhouCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Bochao MaCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Hans R SchölerDepartment for Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
Jinfu NieCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Duanqing PeiCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0002-5222-014X
Xingguo LiuCAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.ORCID 0000-0001-7060-8204
Guangzhou Institutes of Biomedicine and Health · CNAnhui University · CNMax Planck Institute for Molecular Biomedicine · DE
Funding
CAS STS ProgramCAS Youth Innovation Promotion AssociationGrant from Yangtse River Scholar Bonus SchemesGuangdong Province Science and Technology Program 2015TX01R047Guangdong Province Science and Technology Program 2017A020215056Guangdong Province Science and Technology Program 2017B020230005Guangdong Province Science and Technology Program 2017B030314056Guangdong Province Science and Technology Program 2018A030313825Guangdong Province Science and Technology Program 2018GZR110103002Guangzhou Health Care and Cooperative Innovation Major Project 201604020009Guangzhou Health Care and Cooperative Innovation Major Project 201704020218Guangzhou Science and Technology Program 201707010178Guangzhou Science and Technology Program 201807010067the Key Research Program of Frontier Sciences, CAS QYZDB-SSW-SMC001the Key Research Program of Frontier Sciences, CAS QYZDJ-SSW-SMC009the National Key Research and Development Program of China 2016YFA0100300the National Key Research and Development Program of China 2017YFA0102900the National Key Research and Development Program of China 2017YFA0106300the National Key Research and Development Program of China 2017YFA0504100the National Key Research and Development Program of China 2017YFC1001602the National Key Research and Development Program of China 2018YFA0107100the National Natural Science Foundation projects of China 31421004the National Natural Science Foundation projects of China 31530038the National Natural Science Foundation projects of China 31601088the National Natural Science Foundation projects of China 31601176the National Natural Science Foundation projects of China 31622037the National Natural Science Foundation projects of China 31631163001the National Natural Science Foundation projects of China 31701106the National Natural Science Foundation projects of China 31701281the National Natural Science Foundation projects of China 31801168the National Natural Science Foundation projects of China 31830060the National Natural Science Foundation projects of China 31900614the National Natural Science Foundation projects of China 31970709the National Natural Science Foundation projects of China 81570520the National Natural Science Foundation projects of China 81901275the National Natural Science Foundation projects of China U1601227the Strategic Priorty Research Program of the Chinese Academy of Sciences XDA16010505the Strategic Priorty Research Program of the Chinese Academy of Sciences XDA16030505
Abstract
The success of Yamanaka factor reprogramming of somatic cells into induced pluripotent stem cells suggests that some factor(s) must remodel the nuclei from a condensed state to a relaxed state. How factor-dependent chromatin opening occurs remains unclear. Using FRAP and ATAC-seq, we found that Oct4 acts as a pioneer factor that loosens heterochromatin and facilitates the binding of Klf4 and the expression of epithelial genes in early reprogramming, leading to enhanced mesenchymal-to-epithelial transition. A mutation in the Oct4 linker, L80A, which shows impaired interaction with the BAF complex component Brg1, is inactive in heterochromatin loosening. Oct4-L80A also blocks the binding of Klf4 and retards MET. Finally, vitamin C or Gadd45a could rescue the reprogramming deficiency of Oct4-L80A by enhancing chromatin opening and Klf4 binding. These studies reveal a cooperation between Oct4 and Klf4 at the chromatin level that facilitates MET at the cellular level and shed light into the research of multiple factors in cell fate determination.
Indexed as
Cellular ReprogrammingAnimalsAntioxidantsAscorbic AcidCell Cycle ProteinsCell DifferentiationCells, CulturedDNA HelicasesEpithelial CellsEpithelial-Mesenchymal TransitionFibroblastsGADD45 ProteinsHeterochromatinHistonesHumansInduced Pluripotent Stem CellsAntioxidantsAscorbic AcidCell Cycle ProteinsDNA HelicasesGADD45A protein, humanGADD45 ProteinsHeterochromatinhistone H3 trimethyl Lys4HistonesKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsNuclear ProteinsOctamer Transcription Factor-3POU5F1 protein, humanSMARCA4 protein, humanTranscription Factorsheterochromatin looseningKlf4mesenchymal-to-epithelial transitionOct4reprogramming
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