A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress.
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.
Kang
Jinsuk
J
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Gemberling
Matthew
M
Nakamura
Mitsuhiro
M
Whitby
Frank G
FG
Handa
Hiroshi
H
Fairbrother
William G
WG
Tantin
Dean
D
D000595:Amino Acid Sequence; D000818:Animals; D004249:DNA Damage / Q000502:physiology*; D019281:Dimerization; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D055029:Inverted Repeat Sequences / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D050811:Octamer Transcription Factor-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D050811:Octamer Transcription Factor-1; D050814:Octamer Transcription Factor-3