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A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress.
- Source :
-
Genes & development [Genes Dev] 2009 Jan 15; Vol. 23 (2), pp. 208-22. - Publication Year :
- 2009
-
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.
- Subjects :
- Amino Acid Sequence
Animals
Dimerization
HeLa Cells
Humans
Inverted Repeat Sequences genetics
Mice
Models, Molecular
Molecular Sequence Data
Mutation
Octamer Transcription Factor-1 chemistry
Octamer Transcription Factor-1 genetics
Octamer Transcription Factor-3 chemistry
Octamer Transcription Factor-3 genetics
Phosphorylation
Protein Binding
Protein Structure, Tertiary
DNA Damage physiology
Gene Expression Regulation
Octamer Transcription Factor-1 metabolism
Octamer Transcription Factor-3 metabolism
Oxidative Stress physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1549-5477
- Volume :
- 23
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Genes & development
- Publication Type :
- Academic Journal
- Accession number :
- 19171782
- Full Text :
- https://doi.org/10.1101/gad.1750709