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PMID: 19171782 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress.

Genes & development ·Vol. 23 ·No. 2 ·2009-01-15 ·Pages 208-22

Kang J, Gemberling M, Nakamura M, Whitby FG, Handa H, Fairbrother WG, Tantin D

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.

MeSH Terms
Amino Acid Sequence Animals DNA Damage/physiology Dimerization Gene Expression Regulation HeLa Cells Humans Inverted Repeat Sequences/genetics Mice Models, Molecular Molecular Sequence Data Mutation Octamer Transcription Factor-1/chemistry,genetics,metabolism Octamer Transcription Factor-3/chemistry,genetics,metabolism Oxidative Stress/physiology Phosphorylation Protein Binding Protein Structure, Tertiary
Chemicals
Octamer Transcription Factor-1 Octamer Transcription Factor-3
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kang Jinsuk
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Gemberling Matthew
Nakamura Mitsuhiro
Whitby Frank G
Handa Hiroshi
Fairbrother William G
Tantin Dean
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.1750709
Published
2009-01-15
Pages
208-22
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2648538
Subset
IM
Grants
NCI NIH HHS · P30 CA042014 · United States
NCI NIH HHS · P30CA042014 · United States
External Links
PubMed source DOI: 10.1101/gad.1750709 PMC Full Text View journal details
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