Abstract
Embryonic stem (ES) cells offer insight into early developmental fate decisions, and their controlled differentiation may yield vast regenerative potential. The molecular determinants supporting ES cell self-renewal are incompletely understood. The homeodomain proteins Nanog and Oct4 are essential for mouse ES cell self-renewal. Using a high-throughput approach, we discovered DNaseI hypersensitive sites and potential regulatory elements along a 160-kb region of the genome that includes GDF3, Dppa3, and Nanog. We analyzed gene expression, chromatin occupancy, and higher-order chromatin structure throughout this gene locus and found that expression of the reprogramming factor Oct4 is required to maintain its integrity.
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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CCCTC-Binding Factor
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Cell Differentiation / genetics
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Cell Line
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Chromatin / chemistry
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Chromatin / metabolism*
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Chromatin / ultrastructure
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Deoxyribonuclease I / chemistry
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Embryonic Stem Cells / cytology
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Embryonic Stem Cells / metabolism*
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Gene Expression Regulation, Developmental*
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Growth Differentiation Factor 3
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Homeodomain Proteins / genetics*
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Insulator Elements
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Intercellular Signaling Peptides and Proteins / genetics
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Mice
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Nanog Homeobox Protein
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Octamer Transcription Factor-3 / genetics
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Octamer Transcription Factor-3 / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Transcription Factors / metabolism
Substances
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CCCTC-Binding Factor
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Chromatin
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Chromosomal Proteins, Non-Histone
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Ctcf protein, mouse
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DNA-Binding Proteins
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Dppa3 protein, mouse
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Gdf3 protein, mouse
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Growth Differentiation Factor 3
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Homeodomain Proteins
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Intercellular Signaling Peptides and Proteins
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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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Repressor Proteins
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Transcription Factors
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Deoxyribonuclease I