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Pluripotency transcription factor Oct4 mediates stepwise nucleosome demethylation and depletion.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2015 Mar; Vol. 35 (6), pp. 1014-25. Date of Electronic Publication: 2015 Jan 12. - Publication Year :
- 2015
-
Abstract
- The mechanisms whereby the crucial pluripotency transcription factor Oct4 regulates target gene expression are incompletely understood. Using an assay system based on partially differentiated embryonic stem cells, we show that Oct4 opposes the accumulation of local H3K9me2 and subsequent Dnmt3a-mediated DNA methylation. Upon binding DNA, Oct4 recruits the histone lysine demethylase Jmjd1c. Chromatin immunoprecipitation (ChIP) time course experiments identify a stepwise Oct4 mechanism involving Jmjd1c recruitment and H3K9me2 demethylation, transient FACT (facilitates chromatin transactions) complex recruitment, and nucleosome depletion. Genome-wide and targeted ChIP confirms binding of newly synthesized Oct4, together with Jmjd1c and FACT, to the Pou5f1 enhancer and a small number of other Oct4 targets, including the Nanog promoter. Histone demethylation is required for both FACT recruitment and H3 depletion. Jmjd1c is required to induce endogenous Oct4 expression and fully reprogram fibroblasts to pluripotency, indicating that the assay system identifies functional Oct4 cofactors. These findings indicate that Oct4 sequentially recruits activities that catalyze histone demethylation and depletion.<br /> (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- Animals
Cell Differentiation genetics
Cells, Cultured
Chromatin Immunoprecipitation methods
DNA (Cytosine-5-)-Methyltransferases genetics
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Embryonic Stem Cells metabolism
Fibroblasts metabolism
Histones genetics
Histones metabolism
Homeodomain Proteins genetics
Homeodomain Proteins metabolism
Humans
Jumonji Domain-Containing Histone Demethylases genetics
Jumonji Domain-Containing Histone Demethylases metabolism
Mice
Nucleosomes genetics
Octamer Transcription Factor-3 genetics
Promoter Regions, Genetic genetics
Regulatory Sequences, Nucleic Acid genetics
DNA Methylation genetics
Nucleosomes metabolism
Octamer Transcription Factor-3 metabolism
Pluripotent Stem Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 35
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 25582194
- Full Text :
- https://doi.org/10.1128/MCB.01105-14