Transcriptional activation of MYC-induced genes by GCN5 promotes B-cell lymphomagenesis

Aimee T. Farria; Joshua B. Plummer; Andrew P. Salinger; Jianjun Shen; Kevin Lin; Yue Lu; Kevin M. McBride; Evangelia Koutelou; Sharon Y.R. Dent

doi:10.1158/0008-5472.CAN-20-2379

Transcriptional activation of MYC-induced genes by GCN5 promotes B-cell lymphomagenesis

Aimee T. Farria, Joshua B. Plummer, Andrew P. Salinger, Jianjun Shen, Kevin Lin, Yue Lu, Kevin M. McBride, Evangelia Koutelou, Sharon Y.R. Dent

Epigenetics & Molecular Carcinogenesis

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Overexpression of the MYC oncoprotein is an initiating step in the formation of several cancers. MYC frequently recruits chromatin-modifying complexes to DNA to amplify the expression of cancer-promoting genes, including those regulating cell cycle, proliferation, and metabolism, yet the roles of specific modifiers in different cancer types are not well defined. Here, we show that GCN5 is an essential coactivator of cell-cycle gene expression driven by MYC overexpression and that deletion of Gcn5 delays or abrogates tumorigenesis in the Em-Myc mouse model of B-cell lymphoma. Our results demonstrate that Gcn5 loss impacts both expression and downstream functions of Myc. Significance: Our results provide important proof of principle for Gcn5 functions in formation and progression of Myc-driven cancers, suggesting that GCN5 may be a viable target for development of new cancer therapies.

Original language	English (US)
Pages (from-to)	5543-5553
Number of pages	11
Journal	Cancer Research
Volume	80
Issue number	24
DOIs	https://doi.org/10.1158/0008-5472.CAN-20-2379
State	Published - Dec 15 2020

ASJC Scopus subject areas

Oncology
Cancer Research

MD Anderson CCSG core facilities

Science Park Flow Cytometry
Science Park Next-Generation Sequencing Facility
Research Animal Support Facility
Genetically Engineered Mouse Facility

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10.1158/0008-5472.CAN-20-2379

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@article{b05b40d7b29c4597867a40a75583787d,

title = "Transcriptional activation of MYC-induced genes by GCN5 promotes B-cell lymphomagenesis",

abstract = "Overexpression of the MYC oncoprotein is an initiating step in the formation of several cancers. MYC frequently recruits chromatin-modifying complexes to DNA to amplify the expression of cancer-promoting genes, including those regulating cell cycle, proliferation, and metabolism, yet the roles of specific modifiers in different cancer types are not well defined. Here, we show that GCN5 is an essential coactivator of cell-cycle gene expression driven by MYC overexpression and that deletion of Gcn5 delays or abrogates tumorigenesis in the Em-Myc mouse model of B-cell lymphoma. Our results demonstrate that Gcn5 loss impacts both expression and downstream functions of Myc. Significance: Our results provide important proof of principle for Gcn5 functions in formation and progression of Myc-driven cancers, suggesting that GCN5 may be a viable target for development of new cancer therapies.",

author = "Farria, {Aimee T.} and Plummer, {Joshua B.} and Salinger, {Andrew P.} and Jianjun Shen and Kevin Lin and Yue Lu and McBride, {Kevin M.} and Evangelia Koutelou and Dent, {Sharon Y.R.}",

note = "Funding Information: We would like to thank FCCIC and Pam Whitney for her support on flow cytometry experiments. We thank RASF, Amanda Martin, and Tim Macatee for their help with animal husbandry. We would like to thank the Science Park NGS Core for their work on the RNA sequencing, which was supported by Cancer Prevention and Research Institute of Texas Core Facility Support grant (RP170002 to J. Shen). We would also like to thank all members of the Dent laboratory for their advice in experimental procedures. This work was funded by the National Institutes of Health (RO1 GM0677182; R35 GM131678 to S.Y.R. Dent) and the Sowell-Huggins Professorship/Fellowship in Cancer Research (to A.T. Farria and S.Y.R. Dent). Funding Information: A.T. Farria reports grants from NIH NIGMS, CPRIT, as well as other funding from Cancer Answers Foundation and the Sowell and Huggins families during the conduct of the study. S.Y.R. Dent reports grants from NIH during the conduct of the study. No disclosures were reported by the other authors. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",

year = "2020",

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doi = "10.1158/0008-5472.CAN-20-2379",

language = "English (US)",

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pages = "5543--5553",

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T1 - Transcriptional activation of MYC-induced genes by GCN5 promotes B-cell lymphomagenesis

AU - Farria, Aimee T.

AU - Plummer, Joshua B.

AU - Salinger, Andrew P.

AU - Shen, Jianjun

AU - Lin, Kevin

AU - Lu, Yue

AU - McBride, Kevin M.

AU - Koutelou, Evangelia

AU - Dent, Sharon Y.R.

N1 - Funding Information: We would like to thank FCCIC and Pam Whitney for her support on flow cytometry experiments. We thank RASF, Amanda Martin, and Tim Macatee for their help with animal husbandry. We would like to thank the Science Park NGS Core for their work on the RNA sequencing, which was supported by Cancer Prevention and Research Institute of Texas Core Facility Support grant (RP170002 to J. Shen). We would also like to thank all members of the Dent laboratory for their advice in experimental procedures. This work was funded by the National Institutes of Health (RO1 GM0677182; R35 GM131678 to S.Y.R. Dent) and the Sowell-Huggins Professorship/Fellowship in Cancer Research (to A.T. Farria and S.Y.R. Dent). Funding Information: A.T. Farria reports grants from NIH NIGMS, CPRIT, as well as other funding from Cancer Answers Foundation and the Sowell and Huggins families during the conduct of the study. S.Y.R. Dent reports grants from NIH during the conduct of the study. No disclosures were reported by the other authors. Publisher Copyright: © 2020 American Association for Cancer Research.

PY - 2020/12/15

Y1 - 2020/12/15

N2 - Overexpression of the MYC oncoprotein is an initiating step in the formation of several cancers. MYC frequently recruits chromatin-modifying complexes to DNA to amplify the expression of cancer-promoting genes, including those regulating cell cycle, proliferation, and metabolism, yet the roles of specific modifiers in different cancer types are not well defined. Here, we show that GCN5 is an essential coactivator of cell-cycle gene expression driven by MYC overexpression and that deletion of Gcn5 delays or abrogates tumorigenesis in the Em-Myc mouse model of B-cell lymphoma. Our results demonstrate that Gcn5 loss impacts both expression and downstream functions of Myc. Significance: Our results provide important proof of principle for Gcn5 functions in formation and progression of Myc-driven cancers, suggesting that GCN5 may be a viable target for development of new cancer therapies.

AB - Overexpression of the MYC oncoprotein is an initiating step in the formation of several cancers. MYC frequently recruits chromatin-modifying complexes to DNA to amplify the expression of cancer-promoting genes, including those regulating cell cycle, proliferation, and metabolism, yet the roles of specific modifiers in different cancer types are not well defined. Here, we show that GCN5 is an essential coactivator of cell-cycle gene expression driven by MYC overexpression and that deletion of Gcn5 delays or abrogates tumorigenesis in the Em-Myc mouse model of B-cell lymphoma. Our results demonstrate that Gcn5 loss impacts both expression and downstream functions of Myc. Significance: Our results provide important proof of principle for Gcn5 functions in formation and progression of Myc-driven cancers, suggesting that GCN5 may be a viable target for development of new cancer therapies.

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AN - SCOPUS:85100336564

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ER -

Transcriptional activation of MYC-induced genes by GCN5 promotes B-cell lymphomagenesis

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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