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Tuning Transcription Factor Availability through Acetylation-Mediated Genomic Redistribution

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Tuning Transcription Factor Availability through Acetylation-Mediated Genomic Redistribution. / Louphrasitthiphol, Pakavarin; Siddaway, Robert; Loffreda, Alessia; Pogenberg, Vivian; Friedrichsen, Hans; Schepsky, Alexander; Zeng, Zhiqiang; Lu, Min; Strub, Thomas; Freter, Rasmus; Lisle, Richard; Suer, Eda; Thomas, Benjamin; Schuster-Böckler, Benjamin; Filippakopoulos, Panagis; Middleton, Mark; Lu, Xin; Patton, E Elizabeth; Davidson, Irwin; Lambert, Jean-Philippe; Wilmanns, Matthias; Steingrímsson, Eiríkur; Mazza, Davide; Goding, Colin R.

in: MOL CELL, Jahrgang 79, Nr. 3, 06.08.2020, S. 472-487.e10.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Louphrasitthiphol, P, Siddaway, R, Loffreda, A, Pogenberg, V, Friedrichsen, H, Schepsky, A, Zeng, Z, Lu, M, Strub, T, Freter, R, Lisle, R, Suer, E, Thomas, B, Schuster-Böckler, B, Filippakopoulos, P, Middleton, M, Lu, X, Patton, EE, Davidson, I, Lambert, J-P, Wilmanns, M, Steingrímsson, E, Mazza, D & Goding, CR 2020, 'Tuning Transcription Factor Availability through Acetylation-Mediated Genomic Redistribution', MOL CELL, Jg. 79, Nr. 3, S. 472-487.e10. https://doi.org/10.1016/j.molcel.2020.05.025

APA

Louphrasitthiphol, P., Siddaway, R., Loffreda, A., Pogenberg, V., Friedrichsen, H., Schepsky, A., Zeng, Z., Lu, M., Strub, T., Freter, R., Lisle, R., Suer, E., Thomas, B., Schuster-Böckler, B., Filippakopoulos, P., Middleton, M., Lu, X., Patton, E. E., Davidson, I., ... Goding, C. R. (2020). Tuning Transcription Factor Availability through Acetylation-Mediated Genomic Redistribution. MOL CELL, 79(3), 472-487.e10. https://doi.org/10.1016/j.molcel.2020.05.025

Vancouver

Louphrasitthiphol P, Siddaway R, Loffreda A, Pogenberg V, Friedrichsen H, Schepsky A et al. Tuning Transcription Factor Availability through Acetylation-Mediated Genomic Redistribution. MOL CELL. 2020 Aug 6;79(3):472-487.e10. https://doi.org/10.1016/j.molcel.2020.05.025

Bibtex

@article{67c634e4be004f3c8120dd592cb86408,
title = "Tuning Transcription Factor Availability through Acetylation-Mediated Genomic Redistribution",
abstract = "It is widely assumed that decreasing transcription factor DNA-binding affinity reduces transcription initiation by diminishing occupancy of sequence-specific regulatory elements. However, in vivo transcription factors find their binding sites while confronted with a large excess of low-affinity degenerate motifs. Here, using the melanoma lineage survival oncogene MITF as a model, we show that low-affinity binding sites act as a competitive reservoir in vivo from which transcription factors are released by mitogen-activated protein kinase (MAPK)-stimulated acetylation to promote increased occupancy of their regulatory elements. Consequently, a low-DNA-binding-affinity acetylation-mimetic MITF mutation supports melanocyte development and drives tumorigenesis, whereas a high-affinity non-acetylatable mutant does not. The results reveal a paradoxical acetylation-mediated molecular clutch that tunes transcription factor availability via genome-wide redistribution and couples BRAF to tumorigenesis. Our results further suggest that p300/CREB-binding protein-mediated transcription factor acetylation may represent a common mechanism to control transcription factor availability.",
author = "Pakavarin Louphrasitthiphol and Robert Siddaway and Alessia Loffreda and Vivian Pogenberg and Hans Friedrichsen and Alexander Schepsky and Zhiqiang Zeng and Min Lu and Thomas Strub and Rasmus Freter and Richard Lisle and Eda Suer and Benjamin Thomas and Benjamin Schuster-B{\"o}ckler and Panagis Filippakopoulos and Mark Middleton and Xin Lu and Patton, {E Elizabeth} and Irwin Davidson and Jean-Philippe Lambert and Matthias Wilmanns and Eir{\'i}kur Steingr{\'i}msson and Davide Mazza and Goding, {Colin R}",
note = "Copyright {\textcopyright} 2020 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2020",
month = aug,
day = "6",
doi = "10.1016/j.molcel.2020.05.025",
language = "English",
volume = "79",
pages = "472--487.e10",
journal = "MOL CELL",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - Tuning Transcription Factor Availability through Acetylation-Mediated Genomic Redistribution

AU - Louphrasitthiphol, Pakavarin

AU - Siddaway, Robert

AU - Loffreda, Alessia

AU - Pogenberg, Vivian

AU - Friedrichsen, Hans

AU - Schepsky, Alexander

AU - Zeng, Zhiqiang

AU - Lu, Min

AU - Strub, Thomas

AU - Freter, Rasmus

AU - Lisle, Richard

AU - Suer, Eda

AU - Thomas, Benjamin

AU - Schuster-Böckler, Benjamin

AU - Filippakopoulos, Panagis

AU - Middleton, Mark

AU - Lu, Xin

AU - Patton, E Elizabeth

AU - Davidson, Irwin

AU - Lambert, Jean-Philippe

AU - Wilmanns, Matthias

AU - Steingrímsson, Eiríkur

AU - Mazza, Davide

AU - Goding, Colin R

N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2020/8/6

Y1 - 2020/8/6

N2 - It is widely assumed that decreasing transcription factor DNA-binding affinity reduces transcription initiation by diminishing occupancy of sequence-specific regulatory elements. However, in vivo transcription factors find their binding sites while confronted with a large excess of low-affinity degenerate motifs. Here, using the melanoma lineage survival oncogene MITF as a model, we show that low-affinity binding sites act as a competitive reservoir in vivo from which transcription factors are released by mitogen-activated protein kinase (MAPK)-stimulated acetylation to promote increased occupancy of their regulatory elements. Consequently, a low-DNA-binding-affinity acetylation-mimetic MITF mutation supports melanocyte development and drives tumorigenesis, whereas a high-affinity non-acetylatable mutant does not. The results reveal a paradoxical acetylation-mediated molecular clutch that tunes transcription factor availability via genome-wide redistribution and couples BRAF to tumorigenesis. Our results further suggest that p300/CREB-binding protein-mediated transcription factor acetylation may represent a common mechanism to control transcription factor availability.

AB - It is widely assumed that decreasing transcription factor DNA-binding affinity reduces transcription initiation by diminishing occupancy of sequence-specific regulatory elements. However, in vivo transcription factors find their binding sites while confronted with a large excess of low-affinity degenerate motifs. Here, using the melanoma lineage survival oncogene MITF as a model, we show that low-affinity binding sites act as a competitive reservoir in vivo from which transcription factors are released by mitogen-activated protein kinase (MAPK)-stimulated acetylation to promote increased occupancy of their regulatory elements. Consequently, a low-DNA-binding-affinity acetylation-mimetic MITF mutation supports melanocyte development and drives tumorigenesis, whereas a high-affinity non-acetylatable mutant does not. The results reveal a paradoxical acetylation-mediated molecular clutch that tunes transcription factor availability via genome-wide redistribution and couples BRAF to tumorigenesis. Our results further suggest that p300/CREB-binding protein-mediated transcription factor acetylation may represent a common mechanism to control transcription factor availability.

U2 - 10.1016/j.molcel.2020.05.025

DO - 10.1016/j.molcel.2020.05.025

M3 - SCORING: Journal article

C2 - 32531202

VL - 79

SP - 472-487.e10

JO - MOL CELL

JF - MOL CELL

SN - 1097-2765

IS - 3

ER -