Open AccessBcl3 Bridges LIF‐STAT3 to Oct4 Signaling in the Maintenance of Naïve Pluripotency
Author(s) -
Chen ChenYun,
Lee Desy S.,
Yan YuTing,
Shen ChiaNing,
Hwang ShiawMin,
Lee Sho Tone,
Hsieh Patrick C.H.
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2201
Subject(s) - biology , microbiology and biotechnology , leukemia inhibitory factor , stat3 , signal transduction , embryonic stem cell , genetics , gene
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. S tem C ells 2015;33:3468–3480