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Acetylation reprograms MITF target selectivity and residence time

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Acetylation reprograms MITF target selectivity and residence time. / Louphrasitthiphol, Pakavarin; Loffreda, Alessia; Pogenberg, Vivian; Picaud, Sarah; Schepsky, Alexander; Friedrichsen, Hans; Zeng, Zhiqiang; Lashgari, Anahita; Thomas, Benjamin; Patton, E Elizabeth; Wilmanns, Matthias; Filippakopoulos, Panagis; Lambert, Jean-Philippe; Steingrímsson, Eiríkur; Mazza, Davide; Goding, Colin R.

In: NAT COMMUN, Vol. 14, No. 1, 28.09.2023, p. 6051.

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

Harvard

Louphrasitthiphol, P, Loffreda, A, Pogenberg, V, Picaud, S, Schepsky, A, Friedrichsen, H, Zeng, Z, Lashgari, A, Thomas, B, Patton, EE, Wilmanns, M, Filippakopoulos, P, Lambert, J-P, Steingrímsson, E, Mazza, D & Goding, CR 2023, 'Acetylation reprograms MITF target selectivity and residence time', NAT COMMUN, vol. 14, no. 1, pp. 6051. https://doi.org/10.1038/s41467-023-41793-7

APA

Louphrasitthiphol, P., Loffreda, A., Pogenberg, V., Picaud, S., Schepsky, A., Friedrichsen, H., Zeng, Z., Lashgari, A., Thomas, B., Patton, E. E., Wilmanns, M., Filippakopoulos, P., Lambert, J-P., Steingrímsson, E., Mazza, D., & Goding, C. R. (2023). Acetylation reprograms MITF target selectivity and residence time. NAT COMMUN, 14(1), 6051. https://doi.org/10.1038/s41467-023-41793-7

Vancouver

Louphrasitthiphol P, Loffreda A, Pogenberg V, Picaud S, Schepsky A, Friedrichsen H et al. Acetylation reprograms MITF target selectivity and residence time. NAT COMMUN. 2023 Sep 28;14(1):6051. https://doi.org/10.1038/s41467-023-41793-7

Bibtex

@article{50ba1748d0434c7e8ef6c8d07ef2716e,
title = "Acetylation reprograms MITF target selectivity and residence time",
abstract = "The ability of transcription factors to discriminate between different classes of binding sites associated with specific biological functions underpins effective gene regulation in development and homeostasis. How this is achieved is poorly understood. The microphthalmia-associated transcription factor MITF is a lineage-survival oncogene that plays a crucial role in melanocyte development and melanoma. MITF suppresses invasion, reprograms metabolism and promotes both proliferation and differentiation. How MITF distinguishes between differentiation and proliferation-associated targets is unknown. Here we show that compared to many transcription factors MITF exhibits a very long residence time which is reduced by p300/CBP-mediated MITF acetylation at K206. While K206 acetylation also decreases genome-wide MITF DNA-binding affinity, it preferentially directs DNA binding away from differentiation-associated CATGTG motifs toward CACGTG elements. The results reveal an acetylation-mediated switch that suppresses differentiation and provides a mechanistic explanation of why a human K206Q MITF mutation is associated with Waardenburg syndrome.",
keywords = "Humans, Cell Line, Tumor, Microphthalmia-Associated Transcription Factor/genetics, Acetylation, Melanoma/genetics, Melanocytes/metabolism",
author = "Pakavarin Louphrasitthiphol and Alessia Loffreda and Vivian Pogenberg and Sarah Picaud and Alexander Schepsky and Hans Friedrichsen and Zhiqiang Zeng and Anahita Lashgari and Benjamin Thomas and Patton, {E Elizabeth} and Matthias Wilmanns and Panagis Filippakopoulos and Jean-Philippe Lambert and Eir{\'i}kur Steingr{\'i}msson and Davide Mazza and Goding, {Colin R}",
note = "{\textcopyright} 2023. Springer Nature Limited.",
year = "2023",
month = sep,
day = "28",
doi = "10.1038/s41467-023-41793-7",
language = "English",
volume = "14",
pages = "6051",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Acetylation reprograms MITF target selectivity and residence time

AU - Louphrasitthiphol, Pakavarin

AU - Loffreda, Alessia

AU - Pogenberg, Vivian

AU - Picaud, Sarah

AU - Schepsky, Alexander

AU - Friedrichsen, Hans

AU - Zeng, Zhiqiang

AU - Lashgari, Anahita

AU - Thomas, Benjamin

AU - Patton, E Elizabeth

AU - Wilmanns, Matthias

AU - Filippakopoulos, Panagis

AU - Lambert, Jean-Philippe

AU - Steingrímsson, Eiríkur

AU - Mazza, Davide

AU - Goding, Colin R

N1 - © 2023. Springer Nature Limited.

PY - 2023/9/28

Y1 - 2023/9/28

N2 - The ability of transcription factors to discriminate between different classes of binding sites associated with specific biological functions underpins effective gene regulation in development and homeostasis. How this is achieved is poorly understood. The microphthalmia-associated transcription factor MITF is a lineage-survival oncogene that plays a crucial role in melanocyte development and melanoma. MITF suppresses invasion, reprograms metabolism and promotes both proliferation and differentiation. How MITF distinguishes between differentiation and proliferation-associated targets is unknown. Here we show that compared to many transcription factors MITF exhibits a very long residence time which is reduced by p300/CBP-mediated MITF acetylation at K206. While K206 acetylation also decreases genome-wide MITF DNA-binding affinity, it preferentially directs DNA binding away from differentiation-associated CATGTG motifs toward CACGTG elements. The results reveal an acetylation-mediated switch that suppresses differentiation and provides a mechanistic explanation of why a human K206Q MITF mutation is associated with Waardenburg syndrome.

AB - The ability of transcription factors to discriminate between different classes of binding sites associated with specific biological functions underpins effective gene regulation in development and homeostasis. How this is achieved is poorly understood. The microphthalmia-associated transcription factor MITF is a lineage-survival oncogene that plays a crucial role in melanocyte development and melanoma. MITF suppresses invasion, reprograms metabolism and promotes both proliferation and differentiation. How MITF distinguishes between differentiation and proliferation-associated targets is unknown. Here we show that compared to many transcription factors MITF exhibits a very long residence time which is reduced by p300/CBP-mediated MITF acetylation at K206. While K206 acetylation also decreases genome-wide MITF DNA-binding affinity, it preferentially directs DNA binding away from differentiation-associated CATGTG motifs toward CACGTG elements. The results reveal an acetylation-mediated switch that suppresses differentiation and provides a mechanistic explanation of why a human K206Q MITF mutation is associated with Waardenburg syndrome.

KW - Humans

KW - Cell Line, Tumor

KW - Microphthalmia-Associated Transcription Factor/genetics

KW - Acetylation

KW - Melanoma/genetics

KW - Melanocytes/metabolism

U2 - 10.1038/s41467-023-41793-7

DO - 10.1038/s41467-023-41793-7

M3 - SCORING: Journal article

C2 - 37770430

VL - 14

SP - 6051

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -