Gene repression by coactivator repulsion

Kate Senger; Menie Merika; Theodora Agalioti; Junming Yie; Carlos R. Escalante; Guoying Chen; Aneel K. Aggarwal; Dimitris Thanos

doi:10.1016/S1097-2765(05)00081-X

Gene repression by coactivator repulsion

Kate Senger
, Menie Merika
, Theodora Agalioti
, Junming Yie
, Carlos R. Escalante
, Guoying Chen
, Aneel K. Aggarwal
, Dimitris Thanos

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

66 Scopus citations

Abstract

We show that the IRF-2 oncoprotein represses virus-induced IFN-β gene transcription via a novel mechanism. Virus infection induces recruitment of IRF-2 to some part of the endogenous IFN-β enhancers as part of the enhanceosome. Enhanceosomes bearing IRF-2 cannot activate transcription, due to the presence of a domain in IRF-2 that prevents enhanceosome-dependent recruitment of the CBP-Pol II holoenzyme complex. As a consequences, IRF-2 incorporation into enhanceosomes restricts the number of IFN-β promoters directing transcription. Remarkably, deletion of the IRF-2 gene increases IFN-β expression by expanding the number of cells capable of inducing IFN-β gene transcription in response to virus infection.

Original language	English
Pages (from-to)	931-937
Number of pages	7
Journal	Molecular Cell
Volume	6
Issue number	4
DOIs	https://doi.org/10.1016/S1097-2765(05)00081-X
State	Published - 2000

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@article{8f718597935a45d5a92c692376716add,

title = "Gene repression by coactivator repulsion",

abstract = "We show that the IRF-2 oncoprotein represses virus-induced IFN-β gene transcription via a novel mechanism. Virus infection induces recruitment of IRF-2 to some part of the endogenous IFN-β enhancers as part of the enhanceosome. Enhanceosomes bearing IRF-2 cannot activate transcription, due to the presence of a domain in IRF-2 that prevents enhanceosome-dependent recruitment of the CBP-Pol II holoenzyme complex. As a consequences, IRF-2 incorporation into enhanceosomes restricts the number of IFN-β promoters directing transcription. Remarkably, deletion of the IRF-2 gene increases IFN-β expression by expanding the number of cells capable of inducing IFN-β gene transcription in response to virus infection.",

author = "Kate Senger and Menie Merika and Theodora Agalioti and Junming Yie and Escalante, \{Carlos R.\} and Guoying Chen and Aggarwal, \{Aneel K.\} and Dimitris Thanos",

note = "Funding Information: We thank S. J. Weintraub, Y. Chang, P. Moore, J. Hiscott, S. Chellappan, V. Palombella, and T. Maniatis for reagents used in this study. We thank B. Dynlacht, J. Falvo, and B. Parekh for their advice on the chromatin immunoprecipitation experiments. We also thank Tom Maniatis, Richard Mann, and Nikhil Munshi for critical reading of the manuscript and Tada Taniguchi for helpful discussions. This work was supported by grants from the National Institute of Health (1RO1GM54605), the Pew Scholars Program in Biomedical Sciences, the March of Dimes, the Irma T. Hirschl Foundation (to D. T.), and from National Institute of Health (1RO1AI41706) to A. K. A. and D. T.",

year = "2000",

doi = "10.1016/S1097-2765(05)00081-X",

language = "English",

volume = "6",

pages = "931--937",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "4",

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T1 - Gene repression by coactivator repulsion

AU - Senger, Kate

AU - Merika, Menie

AU - Agalioti, Theodora

AU - Yie, Junming

AU - Escalante, Carlos R.

AU - Chen, Guoying

AU - Aggarwal, Aneel K.

AU - Thanos, Dimitris

N1 - Funding Information: We thank S. J. Weintraub, Y. Chang, P. Moore, J. Hiscott, S. Chellappan, V. Palombella, and T. Maniatis for reagents used in this study. We thank B. Dynlacht, J. Falvo, and B. Parekh for their advice on the chromatin immunoprecipitation experiments. We also thank Tom Maniatis, Richard Mann, and Nikhil Munshi for critical reading of the manuscript and Tada Taniguchi for helpful discussions. This work was supported by grants from the National Institute of Health (1RO1GM54605), the Pew Scholars Program in Biomedical Sciences, the March of Dimes, the Irma T. Hirschl Foundation (to D. T.), and from National Institute of Health (1RO1AI41706) to A. K. A. and D. T.

PY - 2000

Y1 - 2000

N2 - We show that the IRF-2 oncoprotein represses virus-induced IFN-β gene transcription via a novel mechanism. Virus infection induces recruitment of IRF-2 to some part of the endogenous IFN-β enhancers as part of the enhanceosome. Enhanceosomes bearing IRF-2 cannot activate transcription, due to the presence of a domain in IRF-2 that prevents enhanceosome-dependent recruitment of the CBP-Pol II holoenzyme complex. As a consequences, IRF-2 incorporation into enhanceosomes restricts the number of IFN-β promoters directing transcription. Remarkably, deletion of the IRF-2 gene increases IFN-β expression by expanding the number of cells capable of inducing IFN-β gene transcription in response to virus infection.

AB - We show that the IRF-2 oncoprotein represses virus-induced IFN-β gene transcription via a novel mechanism. Virus infection induces recruitment of IRF-2 to some part of the endogenous IFN-β enhancers as part of the enhanceosome. Enhanceosomes bearing IRF-2 cannot activate transcription, due to the presence of a domain in IRF-2 that prevents enhanceosome-dependent recruitment of the CBP-Pol II holoenzyme complex. As a consequences, IRF-2 incorporation into enhanceosomes restricts the number of IFN-β promoters directing transcription. Remarkably, deletion of the IRF-2 gene increases IFN-β expression by expanding the number of cells capable of inducing IFN-β gene transcription in response to virus infection.

UR - https://www.scopus.com/pages/publications/0033638002

U2 - 10.1016/S1097-2765(05)00081-X

DO - 10.1016/S1097-2765(05)00081-X

M3 - Article

C2 - 11090630

AN - SCOPUS:0033638002

SN - 1097-2765

VL - 6

SP - 931

EP - 937

JO - Molecular Cell

JF - Molecular Cell

IS - 4

ER -

Gene repression by coactivator repulsion

Abstract

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