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5. A SNAI2/CTCF Interaction is Required for NOTCH1 Expression in Rhabdomyosarcoma

Author

Sreenivas, Prethish, primary, Wang, Long, additional, Wang, Meng, additional, Challa, Anil, additional, Modi, Paulomi, additional, Hensch, Nicole Rae, additional, Gryder, Berkley, additional, Chou, Hsien-Chao, additional, Zhao, Xiang R., additional, Sunkel, Benjamin, additional, Moreno-Campos, Rodrigo, additional, Khan, Javed, additional, Stanton, Benjamin Z., additional, and Ignatius, Myron S., additional

Published
2023
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6. BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma

Author

Laubscher, Dominik, Gryder, Berkley E., Sunkel, Benjamin D., Andresson, Thorkell, Wachtel, Marco, Das, Sudipto, Roschitzki, Bernd, Wolski, Witold, Wu, Xiaoli S., Chou, Hsien-Chao, Song, Young K., Wang, Chaoyu, Wei, Jun S., Wang, Meng, Wen, Xinyu, Ngo, Quy Ai, Marques, Joana G., Vakoc, Christopher R., Schäfer, Beat W., Stanton, Benjamin Z., and Khan, Javed

Published
2021
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7. Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13

Author

Chen, Zhong, Wu, Dayong, Thomas-Ahner, Jennifer M., Lu, Changxue, Zhao, Pei, Zhang, Qingfu, Geraghty, Connor, Yan, Pearlly S., Hankey, William, Sunkel, Benjamin, Cheng, Xiaolong, Antonarakis, Emmanuel S., Wang, Qi-En, Liu, Zhihua, Huang, Tim H.-M., Jin, Victor X., Clinton, Steven K., Luo, Jun, Huang, Jiaoti, and Wang, Qianben

Published
2018

9. Data from SNAI2-Mediated Repression of BIM Protects Rhabdomyosarcoma from Ionizing Radiation

Author

Wang, Long, primary, Hensch, Nicole R., primary, Bondra, Kathryn, primary, Sreenivas, Prethish, primary, Zhao, Xiang R., primary, Chen, Jiangfei, primary, Moreno Campos, Rodrigo, primary, Baxi, Kunal, primary, Vaseva, Angelina V., primary, Sunkel, Benjamin D., primary, Gryder, Berkley E., primary, Pomella, Silvia, primary, Stanton, Benjamin Z., primary, Zheng, Siyuan, primary, Chen, Eleanor Y., primary, Rota, Rossella, primary, Khan, Javed, primary, Houghton, Peter J., primary, and Ignatius, Myron S., primary

Published
2023
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10. Supplementary Tables 1-5 from SNAI2-Mediated Repression of BIM Protects Rhabdomyosarcoma from Ionizing Radiation

Author

Wang, Long, primary, Hensch, Nicole R., primary, Bondra, Kathryn, primary, Sreenivas, Prethish, primary, Zhao, Xiang R., primary, Chen, Jiangfei, primary, Moreno Campos, Rodrigo, primary, Baxi, Kunal, primary, Vaseva, Angelina V., primary, Sunkel, Benjamin D., primary, Gryder, Berkley E., primary, Pomella, Silvia, primary, Stanton, Benjamin Z., primary, Zheng, Siyuan, primary, Chen, Eleanor Y., primary, Rota, Rossella, primary, Khan, Javed, primary, Houghton, Peter J., primary, and Ignatius, Myron S., primary

Published
2023
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11. Supplementary Materials, Methods, and References from SNAI2-Mediated Repression of BIM Protects Rhabdomyosarcoma from Ionizing Radiation

Author

Wang, Long, primary, Hensch, Nicole R., primary, Bondra, Kathryn, primary, Sreenivas, Prethish, primary, Zhao, Xiang R., primary, Chen, Jiangfei, primary, Moreno Campos, Rodrigo, primary, Baxi, Kunal, primary, Vaseva, Angelina V., primary, Sunkel, Benjamin D., primary, Gryder, Berkley E., primary, Pomella, Silvia, primary, Stanton, Benjamin Z., primary, Zheng, Siyuan, primary, Chen, Eleanor Y., primary, Rota, Rossella, primary, Khan, Javed, primary, Houghton, Peter J., primary, and Ignatius, Myron S., primary

Published
2023
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15. Abstract 668: A MYOD-SKP2 axis boosts oncogenic properties of fusion negative rhabdomyosarcoma and is counteracted by neddylation inhibition in vitro and in vivo

Author

Pomella, Silvia, primary, Cassandri, Matteo, additional, Phelps, Doris, additional, Perrone, Clara, additional, Pezzella, Michele, additional, Wachtel, Marco, additional, Sunkel, Benjamin, additional, Cardinale, Antonella, additional, Walters, Zoe, additional, Cossetti, Cristina, additional, Rodriguez, Sonia, additional, Carlesso, Nadia, additional, Shipley, Janet, additional, Miele, Lucio, additional, Schafer, Beat, additional, Velardi, Enrico, additional, Houghton, Peter, additional, Gryder, Berkley, additional, Stanton, Benjamin, additional, Quintarelli, Concetta, additional, De Angelis, Biagio, additional, Locatelli, Franco, additional, and Rota, Rossella, additional

Published
2022
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16. Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation

Author

Chen, Xuyong, primary, Sunkel, Benjamin, additional, Wang, Meng, additional, Kang, Siwen, additional, Wang, Tingting, additional, Gnanaprakasam, J. N. Rashida, additional, Liu, Lingling, additional, Cassel, Teresa A., additional, Scott, David A., additional, Muñoz-Cabello, Ana M., additional, Lopez-Barneo, Jose, additional, Yang, Jun, additional, Lane, Andrew N., additional, Xin, Gang, additional, Stanton, Benjamin Z., additional, Fan, Teresa W.-M., additional, and Wang, Ruoning, additional

Published
2022
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18. Succinate dehydrogenase/complex II is critical for metabolic and epigenetic regulation of T cell proliferation and inflammation

Author

Chen, Xuyong, primary, Sunkel, Benjamin, additional, Wang, Meng, additional, Kang, Siwen, additional, Wang, Tingting, additional, Gnanaprakasam, JN Rashida, additional, Liu, Lingling, additional, Cassel, Teresa A., additional, Scott, David A., additional, Muñoz-Cabello, Ana M., additional, Lopez-Barneo, Jose, additional, Yang, Jun, additional, Lane, Andrew N., additional, Xin, Gang, additional, Stanton, Benjamin, additional, Fan, Teresa W.-M., additional, and Wang, Ruoning, additional

Published
2021
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20. SNAI2-Mediated Repression of BIM Protects Rhabdomyosarcoma from Ionizing Radiation

Author

Wang, Long, primary, Hensch, Nicole R., additional, Bondra, Kathryn, additional, Sreenivas, Prethish, additional, Zhao, Xiang R., additional, Chen, Jiangfei, additional, Moreno Campos, Rodrigo, additional, Baxi, Kunal, additional, Vaseva, Angelina V., additional, Sunkel, Benjamin D., additional, Gryder, Berkley E., additional, Pomella, Silvia, additional, Stanton, Benjamin Z., additional, Zheng, Siyuan, additional, Chen, Eleanor Y., additional, Rota, Rossella, additional, Khan, Javed, additional, Houghton, Peter J., additional, and Ignatius, Myron S., additional

Published
2021
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24. Phosphorylated MED1 links transcription recycling and cancer growth.

Author

Chen, Zhong, Ye, Zhenqing, Soccio, Raymond E, Nakadai, Tomoyoshi, Hankey, William, Zhao, Yue, Huang, Furong, Yuan, Fuwen, Wang, Hongyan, Cui, Zhifen, Sunkel, Benjamin, Wu, Dayong, Dzeng, Richard K, Thomas-Ahner, Jennifer M, Huang, Tim H M, Clinton, Steven K, Huang, Jiaoti, Lazar, Mitchell A, Jin, Victor X, and Roeder, Robert G

Published
2022
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25. BAF complexes drive proliferation and block myogenic differentiation in fusion-positive rhabdomyosarcoma

Author

Laubscher, Dominik, primary, Gryder, Berkley, additional, Sunkel, Benjamin, additional, Andresson, Thorkell, additional, Das, Sudipto, additional, Roschitzki, Bernd, additional, Wolski, Witold, additional, Wu, Xiaoli, additional, Chou, Hsien-chao, additional, Song, Young, additional, Wang, Chaoyu, additional, Wei, Jun, additional, Wang, Meng, additional, Wen, Xinyu, additional, Marques, Joana, additional, Wachtel, Marco, additional, Vakoc, Christopher, additional, Schäfer, Beat, additional, Stanton, Benjamin, additional, and Khan, Javed, additional

Published
2021
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27. The FLI portion of EWS/FLI contributes a transcriptional regulatory function that is distinct and separable from its DNA-binding function in Ewing sarcoma

Author

Boone, Megann A., primary, Taslim, Cenny, additional, Crow, Jesse C., additional, Selich-Anderson, Julia, additional, Showpnil, Iftekhar A., additional, Sunkel, Benjamin D., additional, Wang, Meng, additional, Stanton, Benjamin Z., additional, Theisen, Emily R., additional, and Lessnick, Stephen L., additional

Published
2020
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30. Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence

Author

Sunkel, Benjamin, primary, Wu, Dayong, additional, Chen, Zhong, additional, Wang, Chiou-Miin, additional, Liu, Xiangtao, additional, Ye, Zhenqing, additional, Horning, Aaron M., additional, Liu, Joseph, additional, Mahalingam, Devalingam, additional, Lopez-Nicora, Horacio, additional, Lin, Chun-Lin, additional, Goodfellow, Paul J., additional, Clinton, Steven K., additional, Jin, Victor X., additional, Chen, Chun-Liang, additional, Huang, Tim H.-M., additional, and Wang, Qianben, additional

Published
2017
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32. Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence

Author

Sunkel, Benjamin, primary, Wu, Dayong, additional, Chen, Zhong, additional, Wang, Chiou-Miin, additional, Liu, Xiangtao, additional, Ye, Zhenqing, additional, Horning, Aaron M., additional, Liu, Joseph, additional, Mahalingam, Devalingam, additional, Lopez-Nicora, Horacio, additional, Lin, Chun-Lin, additional, Goodfellow, Paul J., additional, Clinton, Steven K., additional, Jin, Victor X., additional, Chen, Chun-Liang, additional, Huang, Tim H.-M., additional, and Wang, Qianben, additional

Published
2016
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33. Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13.

Author

Zhong Chen, Dayong Wu, Thomas-Ahner, Jennifer M., Changxue Lu, Pei Zhao, Qingfu Zhang, Geraghty, Connor, Yan, Pearlly S., Hankey, William, Sunkel, Benjamin, Xiaolong Cheng, Antonarakis, Emmanuel S., Qi-En Wang, Zhihua Liu, Tim H.-M. Huang, Jin, Victor X., Clinton, Steven K., Jun Luo, Jiaoti Huang, and Qianben Wang

Subjects
CASTRATION-resistant prostate cancer, BIOLOGICAL tags, PROSTATE tumors, ANDROGEN receptors, GENOMES
Abstract

The constitutively active androgen receptor (AR) splice variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC). Although biomarker studies established the role of AR-V7 in resistance to AR-targeting therapies, how AR-V7 mediates genomic functions in CRPC remains largely unknown. Using a ChIP-exo approach, we show AR-V7 binds to distinct genomic regions and recognizes a full-length androgen-responsive element in CRPC cells and patient tissues. Remarkably, we find dramatic differences in AR-V7 cistromes across diverse CRPC cells and patient tissues, regulating different target gene sets involved in CRPC progression. Surprisingly, we discover that HoxB13 is universally required for and colocalizes with AR-V7 binding to open chromatin across CRPC genomes. HoxB13 pioneers AR-V7 binding through direct physical interaction, and collaborates with AR-V7 to up-regulate target oncogenes. Transcriptional coregulation by HoxB13 and AR-V7 was further supported by their coexpression in tumors and circulating tumor cells from CRPC patients. Importantly, HoxB13 silencing significantly decreases CRPC growth through inhibition of AR-V7 oncogenic function. These results identify HoxB13 as a pivotal upstream regulator of AR-V7-driven transcriptomes that are often cell context-dependent in CRPC, suggesting that HoxB13 may serve as a therapeutic target for AR-V7-driven prostate tumors. [ABSTRACT FROM AUTHOR]

Published
2018
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35. Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer

Author

Chen, Zhong, primary, Lan, Xun, additional, Thomas‐Ahner, Jennifer M, additional, Wu, Dayong, additional, Liu, Xiangtao, additional, Ye, Zhenqing, additional, Wang, Liguo, additional, Sunkel, Benjamin, additional, Grenade, Cassandra, additional, Chen, Junsheng, additional, Zynger, Debra L, additional, Yan, Pearlly S, additional, Huang, Jiaoti, additional, Nephew, Kenneth P, additional, Huang, Tim H‐M, additional, Lin, Shili, additional, Clinton, Steven K, additional, Li, Wei, additional, Jin, Victor X, additional, and Wang, Qianben, additional

Published
2014
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42. Agonist and antagonist switch DNA motifs recognized by human androgen receptor in prostate cancer.

Author

Chen, Zhong, Lan, Xun, Thomas‐Ahner, Jennifer M, Wu, Dayong, Liu, Xiangtao, Ye, Zhenqing, Wang, Liguo, Sunkel, Benjamin, Grenade, Cassandra, Chen, Junsheng, Zynger, Debra L, Yan, Pearlly S, Huang, Jiaoti, Nephew, Kenneth P, Huang, Tim H‐M, Lin, Shili, Clinton, Steven K, Li, Wei, Jin, Victor X, and Wang, Qianben

Subjects
TRANSCRIPTION factors, DNA analysis, PROSTATE cancer treatment, ANDROGEN receptors, NUCLEOTIDE sequence, PROTEIN binding
Abstract

Human transcription factors recognize specific DNA sequence motifs to regulate transcription. It is unknown whether a single transcription factor is able to bind to distinctly different motifs on chromatin, and if so, what determines the usage of specific motifs. By using a motif-resolution chromatin immunoprecipitationexonuclease (ChIP-exo) approach, we find that agonist-liganded human androgen receptor (AR) and antagonist-liganded AR bind to two distinctly different motifs, leading to distinct transcriptional outcomes in prostate cancer cells. Further analysis on clinical prostate tissues reveals that the binding of AR to these two distinct motifs is involved in prostate carcinogenesis. Together, these results suggest that unique ligands may switch DNA motifs recognized by ligand-dependent transcription factors in vivo. Our findings also provide a broad mechanistic foundation for understanding ligand-specific induction of gene expression profiles. [ABSTRACT FROM AUTHOR]

Published
2015
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43. Looking Beyond the Androgen Receptor for Transcriptional Drivers of Prostate Cancer

Author

Sunkel, Benjamin Douglas

Subjects
Biochemistry, Biology, Molecular Biology
Abstract

Prostate cancer remains one of the leading causes of cancer-related deaths in American men. Further understanding of prostate carcinogenesis therefore remains a top priority in the cancer research field, and may lead to the development of novel diagnostic and treatment tools. As androgen receptor (AR) is a crucial component in initial, androgen-dependent prostate cancer (ADPC) progression, targeting AR is the current mainstay for combatting the disease in its early stages. However, resistance to AR-targeting therapy too often develops, which results in the lethal, castration-resistant growth phase of the disease. While more potent, second-generation therapies indicated for castration-resistant prostate cancer (CRPC) treatment have reached the clinic, there is still a need to identify therapeutic targets beyond the AR-signaling axis. It is increasingly understood that AR activity occurs in concert with a diverse cohort of pioneer transcription factors and coregulators that define disease stage-specific AR transcriptional output. This effectively produces a moving target and complicates our ability to efficiently observe and disrupt AR activity. Moreover, many of these same factors define the expression of their own clinically relevant gene targets independent of AR. Improving diagnostic and therapeutic success in prostate cancer requires continued focus on defining the fundamental determinants of AR function and the AR-independent transcriptional drivers of this disease.To this end, we began by defining the molecular mechanism underlying GATA2-mediated AR target gene expression in both ADPC and CRPC cells (Chapter 2). Our work supports a tripartite model of GATA2 pioneer factor activity. Firstly, we show that GATA2 supports AR expression. In AR target gene regulatory regions, GATA2 then establishes an accessible chromatin environment for AR binding. Finally, we find that GATA2 preforms regulatory chromatin loops between AR target gene enhancers and promoters. From a genome-wide perspective, these functions universally support AR genomic binding patterns, suggesting a fundamental role for GATA2 in maintaining AR activity across multiple stages of prostate cancer.We went on to conduct an integrated genomic analysis of gene expression profiles defined by the master transcription factors, CREB1 and FoxA1, in the absence of androgen (Chapter 3). These efforts establish a novel role for CREB1 in defining disease-relevant transcription profiles throughout prostate cancer progression. We further show that AR-independent FoxA1 activity involves extensive collaboration with CREB1. Genes sets collaboratively regulated by CREB1 and FoxA1 proved useful as biomarkers for predicting treatment failure among primary prostate cancer patients. Finally, we found that CREB1/FoxA1 target gene expression was sensitive to multiple kinase-inhibiting compounds.In summary, our work provides added evidence for the critical role of factors such as GATA2 in supporting AR activity throughout all stages of prostate cancer. This concept suggests that targeting AR collaborating factors could efficiently abolish genome-wide AR signaling. Finally, we define prognostic gene expression profiles regulated by the collaborative activity of CREB1 and FoxA1. These gene sets may prove effective in indicating sensitivity to future therapies that do not target AR.

Published
2016

44. Highly quantitative measurement of differential protein-genome binding with PerCell chromatin sequencing.

Author

Tallan A, Kucinski J, Sunkel B, Taslim C, LaHaye S, Liu Q, Qi J, Wang M, Kendall GC, and Stanton BZ

Abstract

We report a universal strategy for 2D chromatin sequencing, to increase uniform data analyses and sharing across labs, and to facilitate highly quantitative comparisons across experimental conditions. Within our system, we provide wetlab and drylab tools for researchers to establish and analyze protein-genome binding data with PerCell ChIP-seq. Our methodology is virtually no cost and flexible, enabling rapid, quantitative, internally normalized chromatin sequencing to catalyze project development in a variety of systems, including in vivo zebrafish epigenomics and cancer cell epigenomics. While we highlight utility in these key areas, our methodology is flexible enough such that rapid comparisons of cellular spike-in versus non spike-in are possible, and generalizability to nuclease-based 2D chromatin sequencing would also be possible within the framework of our pipeline. Through the use of well-defined cellular ratios containing orthologous species' chromatin, we enable cross-species comparative epigenomics and highly quantitative low-cost chromatin sequencing with utility across a range of disciplines.

Published
2024
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