An expanded Oct4 interaction network: implications for stem cell biology, development, and disease.
The transcription factor Oct4 is key in embryonic stem cell identity and reprogramming. Insight into its partners should illuminate how the pluripotent state is established and regulated. Here, we identify a considerably expanded set of Oct4-binding proteins in mouse embryonic stem cells. We find that Oct4 associates with a varied set of proteins including regulators of gene expression and modulators of Oct4 function. Half of its partners are transcriptionally regulated by Oct4 itself or other stem cell transcription factors, whereas one-third display a significant change in expression upon cell differentiation. The majority of Oct4-associated proteins studied to date show an early lethal phenotype when mutated. A fraction of the human orthologs is associated with inherited developmental disorders or causative of cancer. The Oct4 interactome provides a resource for dissecting mechanisms of Oct4 function, enlightening the basis of pluripotency and development, and identifying potential additional reprogramming factors.
Pardo
Mercedes
M
Proteomic Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK. Electronic address: mp3@sanger.ac.uk.
Lang
Benjamin
B
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Yu
Lu
L
Proteomic Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.
Prosser
Haydn
H
Mouse Genomics, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.
Bradley
Allan
A
Mouse Genomics, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.
Babu
M Madan
MM
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Choudhary
Jyoti
J
Proteomic Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK. Electronic address: jc4@sanger.ac.uk.
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D004194:Disease; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D018628:Gene Dosage / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D010641:Phenotype; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014158:Transcription, Genetic
D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D011993:Recombinant Fusion Proteins