title: Bcl3 Bridges LIF-STAT3 to Oct4 Signaling in the Maintenance of Naïve Pluripotency.
abstract: Leukemia inhibitory factor (LIF) regulates mouse embryonic stem cell (mESC) pluripotency through STAT3 activation, but the downstream signaling remains largely unelucidated. Using cDNA microarrays, we verified B cell leukemia/lymphoma 3 (Bcl3) as the most significantly downregulated factor following LIF withdrawal in mESCs. Bcl3 knockdown altered mESC morphology, reduced expression of pluripotency genes including Oct4, Sox2, and Nanog, and downregulated DNA binding of acetylated histone 3 and RNA polymerase II on the Oct4 promoter. Conversely, Bcl3 overexpression partially prevented cell differentiation and promoted Oct4 and Nanog promoter activities. Furthermore, coimmunoprecipitation and chromatin immunoprecipitation experiments demonstrated that Bcl3 regulation of mESC pluripotency may be through its association with Oct4 and β-catenin and its promoter binding capability. These results establish that Bcl3 positively regulates pluripotency genes and thus shed light on the mechanism of Bcl3 as a downstream molecule of LIF/STAT3 signaling in pluripotency maintenance.
authors: Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.|Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.
authors: Chen-Yun
authors: CY
authors: Chen
authors: Institute of Clinical Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.
authors: Desy S
authors: DS
authors: Lee
authors: Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.
authors: Yu-Ting
authors: YT
authors: Yan
authors: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors: Chia-Ning
authors: CN
authors: Shen
authors: Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan.
authors: Shiaw-Min
authors: SM
authors: Hwang
authors: Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.
authors: Sho Tone
authors: ST
authors: Lee
authors: Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.|Institute of Biomedical Science, Academia Sinica, Taipei, Taiwan.|Institute of Clinical Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.
authors: Patrick C H
authors: PC
authors: Hsieh
mesh_terms: D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D005786:Gene Expression Regulation; D053605:Leukemia Inhibitory Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014157:Transcription Factors
keywords: Bcl3; Oct4; Pluripotency; STAT3