TRIM24 links a non-canonical histone signature to breast cancer

Wen Wei Tsai; Zhanxin Wang; Teresa T. Yiu; Kadir C. Akdemir; Weiya Xia; Stefan Winter; Cheng Yu Tsai; Xiaobing Shi; Dirk Schwarzer; William Plunkett; Bruce Aronow; Or Gozani; Wolfgang Fischle; Mien Chie Hung; Dinshaw J. Patel; Michelle Craig Barton

doi:10.1038/nature09542

TRIM24 links a non-canonical histone signature to breast cancer

Wen Wei Tsai, Zhanxin Wang, Teresa T. Yiu, Kadir C. Akdemir, Weiya Xia, Stefan Winter, Cheng Yu Tsai, Xiaobing Shi, Dirk Schwarzer, William Plunkett, Bruce Aronow, Or Gozani, Wolfgang Fischle, Mien Chie Hung, Dinshaw J. Patel, Michelle Craig Barton

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Abstract

Recognition of modified histone species by distinct structural domains within reader proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.

Original language	English (US)
Pages (from-to)	927-932
Number of pages	6
Journal	Nature
Volume	468
Issue number	7326
DOIs	https://doi.org/10.1038/nature09542
State	Published - Dec 16 2010
Externally published	Yes

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@article{883e25c28c764a6f9964448bc5c5993e,

title = "TRIM24 links a non-canonical histone signature to breast cancer",

abstract = "Recognition of modified histone species by distinct structural domains within reader proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.",

author = "Tsai, {Wen Wei} and Zhanxin Wang and Yiu, {Teresa T.} and Akdemir, {Kadir C.} and Weiya Xia and Stefan Winter and Tsai, {Cheng Yu} and Xiaobing Shi and Dirk Schwarzer and William Plunkett and Bruce Aronow and Or Gozani and Wolfgang Fischle and Hung, {Mien Chie} and Patel, {Dinshaw J.} and Barton, {Michelle Craig}",

note = "Funding Information: Acknowledgements This work was supported by funds from the National Institutes of Health (NIH GM081627) and the George and Cynthia Mitchell Foundation (to M.C.B.), from NIH (U54 RR025216 and P30DK078392-01) to B.A., from NIH (GM079641) to O.G., from the Sister Institution Fund of China Medical University and Hospital and MDACC to M.-C.H., from the Starr Foundation and the Leukemia and Lymphoma Society to D.J.P., from the Max Planck Society to W.F., and from the NCI Cancer Center (Support Grant) to the UT MD Anderson Cancer Center. W.-W.T. was supported in part by the Sowell-Huggins Foundation; S.W. by a long-term EMBO fellowship; T.T.Y. by T32 HD07325; and K.C.A. by the Center for Cancer Epigenetics. We thank J. Song, D.C. Jamison, A. Dose, Z. Coban and Y. Wei for technical support and assistance. We are grateful to S. Stratton, M. Lee, M. Bedford, G. Lozano, S. Dent, A. Nardulli and members of our laboratories for advice, reagents and discussions.",

year = "2010",

month = dec,

day = "16",

doi = "10.1038/nature09542",

language = "English (US)",

volume = "468",

pages = "927--932",

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number = "7326",

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TY - JOUR

T1 - TRIM24 links a non-canonical histone signature to breast cancer

AU - Tsai, Wen Wei

AU - Wang, Zhanxin

AU - Yiu, Teresa T.

AU - Akdemir, Kadir C.

AU - Xia, Weiya

AU - Winter, Stefan

AU - Tsai, Cheng Yu

AU - Shi, Xiaobing

AU - Schwarzer, Dirk

AU - Plunkett, William

AU - Aronow, Bruce

AU - Gozani, Or

AU - Fischle, Wolfgang

AU - Hung, Mien Chie

AU - Patel, Dinshaw J.

AU - Barton, Michelle Craig

N1 - Funding Information: Acknowledgements This work was supported by funds from the National Institutes of Health (NIH GM081627) and the George and Cynthia Mitchell Foundation (to M.C.B.), from NIH (U54 RR025216 and P30DK078392-01) to B.A., from NIH (GM079641) to O.G., from the Sister Institution Fund of China Medical University and Hospital and MDACC to M.-C.H., from the Starr Foundation and the Leukemia and Lymphoma Society to D.J.P., from the Max Planck Society to W.F., and from the NCI Cancer Center (Support Grant) to the UT MD Anderson Cancer Center. W.-W.T. was supported in part by the Sowell-Huggins Foundation; S.W. by a long-term EMBO fellowship; T.T.Y. by T32 HD07325; and K.C.A. by the Center for Cancer Epigenetics. We thank J. Song, D.C. Jamison, A. Dose, Z. Coban and Y. Wei for technical support and assistance. We are grateful to S. Stratton, M. Lee, M. Bedford, G. Lozano, S. Dent, A. Nardulli and members of our laboratories for advice, reagents and discussions.

PY - 2010/12/16

Y1 - 2010/12/16

N2 - Recognition of modified histone species by distinct structural domains within reader proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.

AB - Recognition of modified histone species by distinct structural domains within reader proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.

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TRIM24 links a non-canonical histone signature to breast cancer

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