Abstract
The regulatory network of factors that center on master transcription factors such as Oct4, Nanog, and Sox2 help maintain embryonic stem (ES) cells and ensure their pluripotency. The target genes of these master transcription factors define the ES cell transcriptional landscape. In this study, we report our findings that Dido1, a target of canonical transcription factors such as Oct4, Sox2, and Nanog, plays an important role in regulating ES cell maintenance. We found that depletion of Dido1 in mouse ES cells led to differentiation, and ectopic expression of Dido1 inhibited differentiation induced by leukemia inhibitory factor withdrawal. We further demonstrated that whereas Nanog and Oct4 could occupy the Dido1 locus and promote its transcription, Dido1 could also target to the loci of pluripotency factors such as Nanog and Oct4 and positively regulate their expression. Through this feedback and feedforward loop, Dido1 is able to regulate self-renewal of mouse ES cells.
Keywords:
Embryonic Stem Cell; Pluripotency; Self-renewal; Signal Transduction; Stem Cells; Transcription Factors; Transcription Regulation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cell Line
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Cell Proliferation / drug effects
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Embryonic Stem Cells / cytology*
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Embryonic Stem Cells / drug effects
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Embryonic Stem Cells / metabolism*
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Feedback, Physiological / drug effects
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Gene Expression Regulation / drug effects
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Homeodomain Proteins / metabolism
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Humans
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Leukemia Inhibitory Factor / pharmacology
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Mice
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Nanog Homeobox Protein
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Octamer Transcription Factor-3 / metabolism
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Pluripotent Stem Cells / cytology
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Pluripotent Stem Cells / drug effects
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Pluripotent Stem Cells / metabolism
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Promoter Regions, Genetic / genetics
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Protein Binding / genetics
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Transcription Factors / deficiency
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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Dido protein, mouse
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Homeodomain Proteins
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Leukemia Inhibitory Factor
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Nanog Homeobox Protein
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Nanog protein, mouse
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Octamer Transcription Factor-3
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Pou5f1 protein, mouse
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Transcription Factors