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A unique Oct4 interface is crucial for reprogramming to pluripotency

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A unique Oct4 interface is crucial for reprogramming to pluripotency. / Esch, Daniel; Vahokoski, Juha; Groves, Matthew R; Pogenberg, Vivian; Cojocaru, Vlad; Vom Bruch, Hermann; Han, Dong; Drexler, Hannes C A; Araúzo-Bravo, Marcos J; Ng, Calista K L; Jauch, Ralf; Wilmanns, Matthias; Schöler, Hans R.

In: NAT CELL BIOL, Vol. 15, No. 3, 03.2013, p. 295-301.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Esch, D, Vahokoski, J, Groves, MR, Pogenberg, V, Cojocaru, V, Vom Bruch, H, Han, D, Drexler, HCA, Araúzo-Bravo, MJ, Ng, CKL, Jauch, R, Wilmanns, M & Schöler, HR 2013, 'A unique Oct4 interface is crucial for reprogramming to pluripotency', NAT CELL BIOL, vol. 15, no. 3, pp. 295-301. https://doi.org/10.1038/ncb2680

APA

Esch, D., Vahokoski, J., Groves, M. R., Pogenberg, V., Cojocaru, V., Vom Bruch, H., Han, D., Drexler, H. C. A., Araúzo-Bravo, M. J., Ng, C. K. L., Jauch, R., Wilmanns, M., & Schöler, H. R. (2013). A unique Oct4 interface is crucial for reprogramming to pluripotency. NAT CELL BIOL, 15(3), 295-301. https://doi.org/10.1038/ncb2680

Vancouver

Esch D, Vahokoski J, Groves MR, Pogenberg V, Cojocaru V, Vom Bruch H et al. A unique Oct4 interface is crucial for reprogramming to pluripotency. NAT CELL BIOL. 2013 Mar;15(3):295-301. https://doi.org/10.1038/ncb2680

Bibtex

@article{eb7c714bdd61489796791a7f46fe958f,
title = "A unique Oct4 interface is crucial for reprogramming to pluripotency",
abstract = "Terminally differentiated cells can be reprogrammed to pluripotency by the forced expression of Oct4, Sox2, Klf4 and c-Myc. However, it remains unknown how this leads to the multitude of epigenetic changes observed during the reprogramming process. Interestingly, Oct4 is the only factor that cannot be replaced by other members of the same family to induce pluripotency. To understand the unique role of Oct4 in reprogramming, we determined the structure of its POU domain bound to DNA. We show that the linker between the two DNA-binding domains is structured as an α-helix and exposed to the protein's surface, in contrast to the unstructured linker of Oct1. Point mutations in this α-helix alter or abolish the reprogramming activity of Oct4, but do not affect its other fundamental properties. On the basis of mass spectrometry studies of the interactome of wild-type and mutant Oct4, we propose that the linker functions as a protein-protein interaction interface and plays a crucial role during reprogramming by recruiting key epigenetic players to Oct4 target genes. Thus, we provide molecular insights to explain how Oct4 contributes to the reprogramming process.",
keywords = "Amino Acid Sequence, Animals, Blotting, Western, Cell Differentiation, Cells, Cultured, Cellular Reprogramming, Crystallography, X-Ray, DNA/genetics, Electrophoretic Mobility Shift Assay, Embryonic Stem Cells/cytology, Epigenesis, Genetic, Fibroblasts/cytology, Humans, Luciferases/metabolism, Mice, Molecular Sequence Data, Octamer Transcription Factor-3/chemistry, Pluripotent Stem Cells/cytology, RNA, Messenger/genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization",
author = "Daniel Esch and Juha Vahokoski and Groves, {Matthew R} and Vivian Pogenberg and Vlad Cojocaru and {Vom Bruch}, Hermann and Dong Han and Drexler, {Hannes C A} and Ara{\'u}zo-Bravo, {Marcos J} and Ng, {Calista K L} and Ralf Jauch and Matthias Wilmanns and Sch{\"o}ler, {Hans R}",
year = "2013",
month = mar,
doi = "10.1038/ncb2680",
language = "English",
volume = "15",
pages = "295--301",
journal = "NAT CELL BIOL",
issn = "1465-7392",
publisher = "NATURE PUBLISHING GROUP",
number = "3",

}

RIS

TY - JOUR

T1 - A unique Oct4 interface is crucial for reprogramming to pluripotency

AU - Esch, Daniel

AU - Vahokoski, Juha

AU - Groves, Matthew R

AU - Pogenberg, Vivian

AU - Cojocaru, Vlad

AU - Vom Bruch, Hermann

AU - Han, Dong

AU - Drexler, Hannes C A

AU - Araúzo-Bravo, Marcos J

AU - Ng, Calista K L

AU - Jauch, Ralf

AU - Wilmanns, Matthias

AU - Schöler, Hans R

PY - 2013/3

Y1 - 2013/3

N2 - Terminally differentiated cells can be reprogrammed to pluripotency by the forced expression of Oct4, Sox2, Klf4 and c-Myc. However, it remains unknown how this leads to the multitude of epigenetic changes observed during the reprogramming process. Interestingly, Oct4 is the only factor that cannot be replaced by other members of the same family to induce pluripotency. To understand the unique role of Oct4 in reprogramming, we determined the structure of its POU domain bound to DNA. We show that the linker between the two DNA-binding domains is structured as an α-helix and exposed to the protein's surface, in contrast to the unstructured linker of Oct1. Point mutations in this α-helix alter or abolish the reprogramming activity of Oct4, but do not affect its other fundamental properties. On the basis of mass spectrometry studies of the interactome of wild-type and mutant Oct4, we propose that the linker functions as a protein-protein interaction interface and plays a crucial role during reprogramming by recruiting key epigenetic players to Oct4 target genes. Thus, we provide molecular insights to explain how Oct4 contributes to the reprogramming process.

AB - Terminally differentiated cells can be reprogrammed to pluripotency by the forced expression of Oct4, Sox2, Klf4 and c-Myc. However, it remains unknown how this leads to the multitude of epigenetic changes observed during the reprogramming process. Interestingly, Oct4 is the only factor that cannot be replaced by other members of the same family to induce pluripotency. To understand the unique role of Oct4 in reprogramming, we determined the structure of its POU domain bound to DNA. We show that the linker between the two DNA-binding domains is structured as an α-helix and exposed to the protein's surface, in contrast to the unstructured linker of Oct1. Point mutations in this α-helix alter or abolish the reprogramming activity of Oct4, but do not affect its other fundamental properties. On the basis of mass spectrometry studies of the interactome of wild-type and mutant Oct4, we propose that the linker functions as a protein-protein interaction interface and plays a crucial role during reprogramming by recruiting key epigenetic players to Oct4 target genes. Thus, we provide molecular insights to explain how Oct4 contributes to the reprogramming process.

KW - Amino Acid Sequence

KW - Animals

KW - Blotting, Western

KW - Cell Differentiation

KW - Cells, Cultured

KW - Cellular Reprogramming

KW - Crystallography, X-Ray

KW - DNA/genetics

KW - Electrophoretic Mobility Shift Assay

KW - Embryonic Stem Cells/cytology

KW - Epigenesis, Genetic

KW - Fibroblasts/cytology

KW - Humans

KW - Luciferases/metabolism

KW - Mice

KW - Molecular Sequence Data

KW - Octamer Transcription Factor-3/chemistry

KW - Pluripotent Stem Cells/cytology

KW - RNA, Messenger/genetics

KW - Real-Time Polymerase Chain Reaction

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sequence Homology, Amino Acid

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

U2 - 10.1038/ncb2680

DO - 10.1038/ncb2680

M3 - SCORING: Journal article

C2 - 23376973

VL - 15

SP - 295

EP - 301

JO - NAT CELL BIOL

JF - NAT CELL BIOL

SN - 1465-7392

IS - 3

ER -