A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress
- 15 January 2009
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 23 (2), 208-222
- https://doi.org/10.1101/gad.1750709
Abstract
Oct1 and Oct4 are homologous transcription factors with similar DNA-binding specificities. Here we show that Oct1 is dynamically phosphorylated in vivo following exposure of cells to oxidative and genotoxic stress. We further show that stress regulates the selectivity of both proteins for specific DNA sequences. Mutation of conserved phosphorylation target DNA-binding domain residues in Oct1, and Oct4 confirms their role in regulating binding selectivity. Using chromatin immunoprecipitation, we show that association of Oct4 and Oct1 with a distinct group of in vivo targets is inducible by stress, and that Oct1 is essential for a normal post-stress transcriptional response. Finally, using an unbiased Oct1 target screen we identify a large number of genes targeted by Oct1 specifically under conditions of stress, and show that several of these inducible Oct1 targets are also inducibly bound by Oct4 in embryonic stem cells following stress exposure.Keywords
This publication has 63 references indexed in Scilit:
- Identification of Pou5f1, Sox2, and Nanog downstream target genes with statistical confidence by applying a novel algorithm to time course microarray and genome-wide chromatin immunoprecipitation dataBMC Genomics, 2008
- Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem CellsCell, 2008
- Transcription profiling of lung adenocarcinomas of c-myc-transgenic mice: Identification of the c-myc regulatory gene networkBMC Systems Biology, 2008
- High-throughput biochemical analysis of in vivo location data reveals novel distinct classes of POU5F1(Oct4)/DNA complexesGenome Research, 2008
- Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined FactorsCell, 2007
- Differential Effects of Phosphorylation on DNA Binding Properties of N Oct-3 Are Dictated by Protein/DNA Complex StructuresJournal of Molecular Biology, 2007
- Generation of germline-competent induced pluripotent stem cellsNature, 2007
- The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cellsNature Genetics, 2006
- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem CellsCell, 2005
- Cofactor Dynamics and Sufficiency in Estrogen Receptor–Regulated TranscriptionCell, 2000