title: CIBZ Regulates Mesodermal and Cardiac Differentiation of by Suppressing T and Mesp1 Expression in Mouse Embryonic Stem Cells.
abstract: The molecular mechanisms underlying mesodermal and cardiac specification from embryonic stem cells (ESCs) are not fully understood. Here, we showed that the BTB domain-containing zinc finger protein CIBZ is expressed in mouse ESCs but is dramatically downregulated during ESC differentiation. CIBZ deletion in ESCs induced specification toward mesoderm phenotypes and their differentiation into cardiomyocytes, whereas overexpression of CIBZ delayed these processes. During ESC differentiation, CIBZ loss-and-gain-of-function data indicate that CIBZ negatively regulates the expressions of Brachyury (T) and Mesp1, the key transcriptional factors responsible for the specification of mammalian mesoderm and cardiac progenitors, respectively. Chromatin immunoprecipitation assays showed that CIBZ binds to T and Mesp1 promoters in undifferentiated ESCs, and luciferase assays indicate that CIBZ suppresses T and Mesp1 promoters. These findings demonstrate that CIBZ is a novel regulator of mesodermal and cardiac differentiation of ESCs, and suggest that CIBZ-mediated cardiac differentiation depends on the regulation of these two genes.
authors.affiliation: Cell Seed Inc., Tokyo, 135-0064, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kotoku
authors.affiliation: Division of Gene Function in Animals, Nara Institute of Science and Technology, Ikoma, 630-0192, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kosaka
authors.affiliation: Functional Genomics and Medicine, Nara Institute of Science and Technology, Ikoma, 630-0192, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Nishio
authors.affiliation: Functional Genomics and Medicine, Nara Institute of Science and Technology, Ikoma, 630-0192, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Ishida
authors.affiliation: Division of Gene Function in Animals, Nara Institute of Science and Technology, Ikoma, 630-0192, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawaichi
authors.affiliation: Division of Gene Function in Animals, Nara Institute of Science and Technology, Ikoma, 630-0192, Japan.
authors.forename: Eishou
authors.initials: E
authors.lastname: Matsuda