SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response
Summary: The TET2 DNA dioxygenase regulates gene expression by catalyzing demethylation of 5-methylcytosine, thus epigenetically modulating the genome. TET2 does not contain a sequence-specific DNA-binding domain, and how it is recruited to specific genomic sites is not fully understood. Here we car...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718316048 |
| _version_ | 1818036974583283712 |
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| author | Lei-Lei Chen Huai-Peng Lin Wen-Jie Zhou Chen-Xi He Zhi-Yong Zhang Zhou-Li Cheng Jun-Bin Song Peng Liu Xin-Yu Chen Yu-Kun Xia Xiu-Fei Chen Ren-Qiang Sun Jing-Ye Zhang Yi-Ping Sun Lei Song Bing-Jie Liu Rui-Kai Du Chen Ding Fei Lan Sheng-Lin Huang Feng Zhou Suling Liu Yue Xiong Dan Ye Kun-Liang Guan |
| author_facet | Lei-Lei Chen Huai-Peng Lin Wen-Jie Zhou Chen-Xi He Zhi-Yong Zhang Zhou-Li Cheng Jun-Bin Song Peng Liu Xin-Yu Chen Yu-Kun Xia Xiu-Fei Chen Ren-Qiang Sun Jing-Ye Zhang Yi-Ping Sun Lei Song Bing-Jie Liu Rui-Kai Du Chen Ding Fei Lan Sheng-Lin Huang Feng Zhou Suling Liu Yue Xiong Dan Ye Kun-Liang Guan |
| author_sort | Lei-Lei Chen |
| collection | DOAJ |
| description | Summary: The TET2 DNA dioxygenase regulates gene expression by catalyzing demethylation of 5-methylcytosine, thus epigenetically modulating the genome. TET2 does not contain a sequence-specific DNA-binding domain, and how it is recruited to specific genomic sites is not fully understood. Here we carried out a mammalian two-hybrid screen and identified multiple transcriptional regulators potentially interacting with TET2. The SMAD nuclear interacting protein 1 (SNIP1) physically interacts with TET2 and bridges TET2 to bind several transcription factors, including c-MYC. SNIP1 recruits TET2 to the promoters of c-MYC target genes, including those involved in DNA damage response and cell viability. TET2 protects cells from DNA damage-induced apoptosis dependending on SNIP1. Our observations uncover a mechanism for targeting TET2 to specific promoters through a ternary interaction with a co-activator and many sequence-specific DNA-binding factors. This study also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response, thereby connecting epigenetic control to maintenance of genome stability. : Chen et al. show SNIP1 recruits TET2 to the promoters of c-MYC target genes, including those involved in DNA damage response and cell viability. This study uncovers a mechanism for targeting TET2 to specific promoters through a ternary interaction with a co-activator and sequence-specific DNA-binding factors and also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response, thereby connecting epigenetic control to maintenance of genome stability. Keywords: TET2, SNIP1, c-MYC, DNA demethylation, transcription, DNA damage, cell death |
| first_indexed | 2024-12-10T07:19:28Z |
| format | Article |
| id | doaj.art-a38b69ee11dc4a5bbd542e636aef89a7 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T07:19:28Z |
| publishDate | 2018-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a38b69ee11dc4a5bbd542e636aef89a72022-12-22T01:57:51ZengElsevierCell Reports2211-12472018-11-0125614851500.e4SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage ResponseLei-Lei Chen0Huai-Peng Lin1Wen-Jie Zhou2Chen-Xi He3Zhi-Yong Zhang4Zhou-Li Cheng5Jun-Bin Song6Peng Liu7Xin-Yu Chen8Yu-Kun Xia9Xiu-Fei Chen10Ren-Qiang Sun11Jing-Ye Zhang12Yi-Ping Sun13Lei Song14Bing-Jie Liu15Rui-Kai Du16Chen Ding17Fei Lan18Sheng-Lin Huang19Feng Zhou20Suling Liu21Yue Xiong22Dan Ye23Kun-Liang Guan24Huashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Medical College of Xiamen University, Xiamen 361102, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for National Center for Protein Science (The PHOENIX Center), Beijing, ChinaFudan University Shanghai Cancer Center, Key Laboratory of Breast Cancer in Shanghai, Innovation Center for Cell Signaling Network, Cancer Institutes, Fudan University, Shanghai, ChinaFudan University Shanghai Cancer Center, Key Laboratory of Breast Cancer in Shanghai, Innovation Center for Cell Signaling Network, Cancer Institutes, Fudan University, Shanghai, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, National Center for National Center for Protein Science (The PHOENIX Center), Beijing, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaFudan University Shanghai Cancer Center, Key Laboratory of Breast Cancer in Shanghai, Innovation Center for Cell Signaling Network, Cancer Institutes, Fudan University, Shanghai, ChinaHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Corresponding authorHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China; Corresponding authorHuashan Hospital and Key Laboratory of Medical Epigenetics and Metabolism and Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA; Corresponding authorSummary: The TET2 DNA dioxygenase regulates gene expression by catalyzing demethylation of 5-methylcytosine, thus epigenetically modulating the genome. TET2 does not contain a sequence-specific DNA-binding domain, and how it is recruited to specific genomic sites is not fully understood. Here we carried out a mammalian two-hybrid screen and identified multiple transcriptional regulators potentially interacting with TET2. The SMAD nuclear interacting protein 1 (SNIP1) physically interacts with TET2 and bridges TET2 to bind several transcription factors, including c-MYC. SNIP1 recruits TET2 to the promoters of c-MYC target genes, including those involved in DNA damage response and cell viability. TET2 protects cells from DNA damage-induced apoptosis dependending on SNIP1. Our observations uncover a mechanism for targeting TET2 to specific promoters through a ternary interaction with a co-activator and many sequence-specific DNA-binding factors. This study also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response, thereby connecting epigenetic control to maintenance of genome stability. : Chen et al. show SNIP1 recruits TET2 to the promoters of c-MYC target genes, including those involved in DNA damage response and cell viability. This study uncovers a mechanism for targeting TET2 to specific promoters through a ternary interaction with a co-activator and sequence-specific DNA-binding factors and also reveals a TET2-SNIP1-c-MYC pathway in mediating DNA damage response, thereby connecting epigenetic control to maintenance of genome stability. Keywords: TET2, SNIP1, c-MYC, DNA demethylation, transcription, DNA damage, cell deathhttp://www.sciencedirect.com/science/article/pii/S2211124718316048 |
| spellingShingle | Lei-Lei Chen Huai-Peng Lin Wen-Jie Zhou Chen-Xi He Zhi-Yong Zhang Zhou-Li Cheng Jun-Bin Song Peng Liu Xin-Yu Chen Yu-Kun Xia Xiu-Fei Chen Ren-Qiang Sun Jing-Ye Zhang Yi-Ping Sun Lei Song Bing-Jie Liu Rui-Kai Du Chen Ding Fei Lan Sheng-Lin Huang Feng Zhou Suling Liu Yue Xiong Dan Ye Kun-Liang Guan SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response Cell Reports |
| title | SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response |
| title_full | SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response |
| title_fullStr | SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response |
| title_full_unstemmed | SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response |
| title_short | SNIP1 Recruits TET2 to Regulate c-MYC Target Genes and Cellular DNA Damage Response |
| title_sort | snip1 recruits tet2 to regulate c myc target genes and cellular dna damage response |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718316048 |
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