Molecular basis for human respiratory syncytial virus transcriptional regulator NS1 interactions with MED25

Kalita, Parismita; Khatavkar, Oam; Uwase, Grace; Korshunova, Yulia; Hu, Yuying; Wagner, Nicole D.; Xu, Jian; Pan, Jiehong; Nix, Jay C.; Gross, Michael L.; Brody, Steven L.; Borek, Dominika; Amarasinghe, Gaya K.; Payton, Jacqueline E.; Leung, Daisy W.

doi:10.1038/s41467-025-58216-4

Title: Molecular basis for human respiratory syncytial virus transcriptional regulator NS1 interactions with MED25

Journal Article · 24 March 2025 · Nature Communications

DOI: https://doi.org/10.1038/s41467-025-58216-4 · OSTI ID:2553928

Kalita, Parismita ^[1]; Khatavkar, Oam ^[1]; Uwase, Grace ^[1]; Korshunova, Yulia ^[1]; Hu, Yuying ^[1]; Wagner, Nicole D. ^[1];

^[1]; Pan, Jiehong ^[1];

^[2];

^[3];

^[1]; Borek, Dominika ^[4];

^[1];

^[1]

Washington Univ., St. Louis, MO (United States). School of Medicine
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)
Washington Univ., St. Louis, MO (United States)
Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

The Mediator complex facilitates interactions between transcription factors and RNA polymerase II, a process that is required for host gene transcription, including in response to viral infections. Among the many subunits in the Mediator complex, the MED25 subunit has been shown to be a target for viral activators during infection. Here we provide the molecular basis for the interaction between human respiratory syncytial virus (hRSV) nonstructural 1 protein (NS1) and the activator interaction domain (ACID) of MED25. The X-ray crystal structure of the complex revealed that NS1 straddles and binds two faces of MED25 ACID. This interaction is distinct from previously known viral activators. Importantly, our data support the conformational flexibility of viral transcriptional regulators. Furthermore, ChIP-seq and RNA-seq analysis identified the ATF3 transcription factor and a role for NS1/Mediator/ATF3 interaction in host gene regulation in hRSV infections. Our findings provide a molecular basis for hRSV NS1-based regulation of host gene transcription and reveal how viruses exploit the conformational heterogeneity at fuzzy transcription activator interfaces.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS)

Sponsoring Organization:: National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2553928

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 16; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (78)

Mortality Associated With Influenza and Respiratory Syncytial Virus in the United States Thompson, William W.; Shay, David K.; Weintraub, Eric JAMA, Vol. 289, Issue 2 https://doi.org/10.1001/jama.289.2.179	journal	January 2003
Mortality Associated With Influenza and Respiratory Syncytial Virus in the US, 1999-2018 Hansen, Chelsea L.; Chaves, Sandra S.; Demont, Clarisse JAMA Network Open, Vol. 5, Issue 2 https://doi.org/10.1001/jamanetworkopen.2022.0527	journal	February 2022
Exploring Epigenomic Datasets by ChIPseeker Wang, Qianwen; Li, Ming; Wu, Tianzhi Current Protocols, Vol. 2, Issue 10 https://doi.org/10.1002/cpz1.585	journal	October 2022
Activating transcription factor 3 (ATF3) protects against lipopolysaccharide‐induced acute lung injury via inhibiting the expression of TL1A Qian, Lanlan; Zhao, Yunfeng; Guo, Liang Journal of Cellular Physiology, Vol. 232, Issue 12 https://doi.org/10.1002/jcp.25849	journal	May 2017
Shape Complementarity at Protein/Protein Interfaces Lawrence, Michael C.; Colman, Peter M. Journal of Molecular Biology, Vol. 234, Issue 4 https://doi.org/10.1006/jmbi.1993.1648	journal	December 1993
ATF3 transcription factor and its emerging roles in immunity and cancer Thompson, Matthew R.; Xu, Dakang; Williams, Bryan R. G. Journal of Molecular Medicine, Vol. 87, Issue 11 https://doi.org/10.1007/s00109-009-0520-x	journal	August 2009
Solution NMR structure of MED25(391–543) comprising the activator-interacting domain (ACID) of human mediator subunit 25 Eletsky, Alexander; Ruyechan, William T.; Xiao, Rong Journal of Structural and Functional Genomics, Vol. 12, Issue 3 https://doi.org/10.1007/s10969-011-9115-1	journal	July 2011
The interpretation of protein structures: Estimation of static accessibility Lee, B.; Richards, F. M. Journal of Molecular Biology, Vol. 55, Issue 3 https://doi.org/10.1016/0022-2836(71)90324-X	journal	February 1971
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Human Virus Transcriptional Regulators Liu, Xing; Hong, Ted; Parameswaran, Sreeja Cell, Vol. 182, Issue 1 https://doi.org/10.1016/j.cell.2020.06.023	journal	July 2020
Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription Pei, Jingjing; Beri, Nina R.; Zou, Angela J. Cell Reports, Vol. 37, Issue 2 https://doi.org/10.1016/j.celrep.2021.109803	journal	October 2021
Transcriptional responses to injury of regenerative lung alveolar epithelium Ali, Mir; LaCanna, Ryan; Lian, Zhaorui iScience, Vol. 25, Issue 8 https://doi.org/10.1016/j.isci.2022.104843	journal	August 2022
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
Respiratory Syncytial Virus NS1 Protein Targets the Transactivator Binding Domain of MED25 Dong, Jiawei; Basse, Vincent; Bierre, Maxime Journal of Molecular Biology, Vol. 434, Issue 19 https://doi.org/10.1016/j.jmb.2022.167763	journal	October 2022
NMR structure of the human Mediator MED25 ACID domain Bontems, François; Verger, Alexis; Dewitte, Frédérique Journal of Structural Biology, Vol. 174, Issue 1 https://doi.org/10.1016/j.jsb.2010.10.011	journal	April 2011
Protein binding specificity versus promiscuity Schreiber, Gideon; Keating, Amy E. Current Opinion in Structural Biology, Vol. 21, Issue 1 https://doi.org/10.1016/j.sbi.2010.10.002	journal	February 2011
Mediator and the mechanism of transcriptional activation Kornberg, Roger D. Trends in Biochemical Sciences, Vol. 30, Issue 5 https://doi.org/10.1016/j.tibs.2005.03.011	journal	May 2005
Viral degradasome hijacks mitochondria to suppress innate immunity Goswami, Ramansu; Majumdar, Tanmay; Dhar, Jayeeta Cell Research, Vol. 23, Issue 8 https://doi.org/10.1038/cr.2013.98	journal	July 2013
Fast gapped-read alignment with Bowtie 2 Langmead, Ben; Salzberg, Steven L. Nature Methods, Vol. 9, Issue 4 https://doi.org/10.1038/nmeth.1923	journal	March 2012
Structural basis for human respiratory syncytial virus NS1-mediated modulation of host responses Chatterjee, Srirupa; Luthra, Priya; Esaulova, Ekaterina Nature Microbiology, Vol. 2, Issue 9 https://doi.org/10.1038/nmicrobiol.2017.101	journal	June 2017
Transcription regulation by the Mediator complex Soutourina, Julie Nature Reviews Molecular Cell Biology, Vol. 19, Issue 4 https://doi.org/10.1038/nrm.2017.115	journal	December 2017
Structure and VP16 binding of the Mediator Med25 activator interaction domain Vojnic, Erika; Mourão, André; Seizl, Martin Nature Structural & Molecular Biology, Vol. 18, Issue 4 https://doi.org/10.1038/nsmb.1997	journal	March 2011
Structure of the VP16 transactivator target in the Mediator Milbradt, Alexander G.; Kulkarni, Madhura; Yi, Tingfang Nature Structural & Molecular Biology, Vol. 18, Issue 4 https://doi.org/10.1038/nsmb.1999	journal	March 2011
ATF3 promotes erastin-induced ferroptosis by suppressing system Xc– Wang, Liyuan; Liu, Yichen; Du, Tingting Cell Death & Differentiation, Vol. 27, Issue 2 https://doi.org/10.1038/s41418-019-0380-z	journal	July 2019
The Mediator complex as a master regulator of transcription by RNA polymerase II Richter, William F.; Nayak, Shraddha; Iwasa, Janet Nature Reviews Molecular Cell Biology, Vol. 23, Issue 11 https://doi.org/10.1038/s41580-022-00498-3	journal	June 2022
Structure of the human Mediator–RNA polymerase II pre-initiation complex Rengachari, Srinivasan; Schilbach, Sandra; Aibara, Shintaro Nature, Vol. 594, Issue 7861 https://doi.org/10.1038/s41586-021-03555-7	journal	April 2021
Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis van Dam, Hans; Castellazzi, Marc Oncogene, Vol. 20, Issue 19 https://doi.org/10.1038/sj.onc.1204239	journal	April 2001
Close encounters of many kinds: Fos-Jun interactions that mediate transcription regulatory specificity Chinenov, Yurii; Kerppola, Tom K. Oncogene, Vol. 20, Issue 19 https://doi.org/10.1038/sj.onc.1204385	journal	April 2001
Activating transcription factor 3 represses inflammatory responses by binding to the p65 subunit of NF-κB Kwon, Ji-Woong; Kwon, Hyuk-Kwon; Shin, Hyeon-Jun Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep14470	journal	September 2015
Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults Papi, Alberto; Ison, Michael G.; Langley, Joanne M. New England Journal of Medicine, Vol. 388, Issue 7 https://doi.org/10.1056/NEJMoa2209604	journal	February 2023
Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults Walsh, Edward E.; Pérez Marc, Gonzalo; Zareba, Agnieszka M. New England Journal of Medicine, Vol. 388, Issue 16 https://doi.org/10.1056/NEJMoa2213836	journal	April 2023
Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants Kampmann, Beate; Madhi, Shabir A.; Munjal, Iona New England Journal of Medicine, Vol. 388, Issue 16 https://doi.org/10.1056/NEJMoa2216480	journal	April 2023
Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults Wilson, Eleanor; Goswami, Jaya; Baqui, Abdullah H. New England Journal of Medicine, Vol. 389, Issue 24 https://doi.org/10.1056/NEJMoa2307079	journal	December 2023
Surface features of a Mononegavirales matrix protein indicate sites of membrane interaction Money, V. A.; McPhee, H. K.; Mosely, J. A. Proceedings of the National Academy of Sciences, Vol. 106, Issue 11 https://doi.org/10.1073/pnas.0805740106	journal	February 2009
Electrostatics tunes protein interactions to context Fuxreiter, Monika Proceedings of the National Academy of Sciences, Vol. 119, Issue 31 https://doi.org/10.1073/pnas.2209201119	journal	July 2022
ATF3 Gene Liang, Guosheng; Wolfgang, Curt D.; Chen, Benjamin P. C. Journal of Biological Chemistry, Vol. 271, Issue 3 https://doi.org/10.1074/jbc.271.3.1695	journal	January 1996
Transcriptional Autorepression of the Stress-inducible GeneATF3 Wolfgang, Curt D.; Liang, Guosheng; Okamoto, Yoshichika Journal of Biological Chemistry, Vol. 275, Issue 22 https://doi.org/10.1074/jbc.M909637199	journal	June 2000
Pathogenicity and virulence of human respiratory syncytial virus: Multifunctional nonstructural proteins NS1 and NS2 Merritt, Trudy N.; Pei, Jingjing; Leung, Daisy W. Virulence https://doi.org/10.1080/21505594.2023.2283897	journal	November 2023
BEDTools: a flexible suite of utilities for comparing genomic features Quinlan, Aaron R.; Hall, Ira M. Bioinformatics, Vol. 26, Issue 6 https://doi.org/10.1093/bioinformatics/btq033	journal	January 2010
Incidence of Respiratory Syncytial Virus Infection Among Hospitalized Adults, 2017–2020 Branche, Angela R.; Saiman, Lisa; Walsh, Edward E. Clinical Infectious Diseases, Vol. 74, Issue 6 https://doi.org/10.1093/cid/ciab595	journal	July 2021
Respiratory Syncytial Virus–Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis McLaughlin, John M.; Khan, Farid; Schmitt, Heinz-Josef The Journal of Infectious Diseases, Vol. 225, Issue 6 https://doi.org/10.1093/infdis/jiaa752	journal	December 2020
ATF3 Confers Resistance to Pneumococcal Infection Through Positive Regulation of Cytokine Production Nguyen, Cuong Thach; Kim, Eun-Hye; Luong, Truc Thanh The Journal of Infectious Diseases, Vol. 210, Issue 11 https://doi.org/10.1093/infdis/jiu352	journal	June 2014
ReMap 2022: a database of Human, Mouse, Drosophila and Arabidopsis regulatory regions from an integrative analysis of DNA-binding sequencing experiments Hammal, Fayrouz; de Langen, Pierre; Bergon, Aurélie Nucleic Acids Research, Vol. 50, Issue D1, p. D316-D325 https://doi.org/10.1093/nar/gkab996	journal	November 2021
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Refinement of Macromolecular Structures by the Maximum-Likelihood Method Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Acta Crystallographica Section D Biological Crystallography, Vol. 53, Issue 3 https://doi.org/10.1107/S0907444996012255	journal	May 1997
The CCP4 suite: integrative software for macromolecular crystallography Agirre, Jon; Atanasova, Mihaela; Bagdonas, Haroldas Acta Crystallographica Section D Structural Biology, Vol. 79, Issue 6 https://doi.org/10.1107/S2059798323003595	journal	May 2023
Estimates of mortality attributable to influenza and RSV in the United States during 1997–2009 by influenza type or subtype, age, cause of death, and risk status Matias, Gonçalo; Taylor, Robert; Haguinet, François Influenza and Other Respiratory Viruses, Vol. 8, Issue 5 https://doi.org/10.1111/irv.12258	journal	June 2014
Structure of the human Mediator-bound transcription preinitiation complex Abdella, R.; Talyzina, A.; Chen, S. Science, Vol. 372, Issue 6537 https://doi.org/10.1126/science.abg3074	journal	April 2021
Analysis of the Varicella-Zoster Virus IE62 N-Terminal Acidic Transactivating Domain and Its Interaction with the Human Mediator Complex Yamamoto, Shinobu; Eletsky, Alexander; Szyperski, Thomas Journal of Virology, Vol. 83, Issue 12 https://doi.org/10.1128/JVI.00054-09	journal	June 2009
Multiple Functional Domains and Complexes of the Two Nonstructural Proteins of Human Respiratory Syncytial Virus Contribute to Interferon Suppression and Cellular Location Swedan, S.; Andrews, J.; Majumdar, T. Journal of Virology, Vol. 85, Issue 19 https://doi.org/10.1128/JVI.00413-11	journal	July 2011
The Interactome of the Human Respiratory Syncytial Virus NS1 Protein Highlights Multiple Effects on Host Cell Biology Wu, W.; Tran, K. C.; Teng, M. N. Journal of Virology, Vol. 86, Issue 15 https://doi.org/10.1128/JVI.00460-12	journal	May 2012
Respiratory Syncytial Virus Nonstructural Proteins Decrease Levels of Multiple Members of the Cellular Interferon Pathways Swedan, Samer; Musiyenko, Alla; Barik, Sailen Journal of Virology, Vol. 83, Issue 19 https://doi.org/10.1128/JVI.00715-09	journal	July 2009
Varicella-Zoster Virus IE62 Protein Utilizes the Human Mediator Complex in Promoter Activation Yang, Min; Hay, John; Ruyechan, William T. Journal of Virology, Vol. 82, Issue 24 https://doi.org/10.1128/JVI.01693-08	journal	December 2008
Suppression of the Induction of Alpha, Beta, and Gamma Interferons by the NS1 and NS2 Proteins of Human Respiratory Syncytial Virus in Human Epithelial Cells and Macrophages Spann, Kirsten M.; Tran, Kim-C.; Chi, Bo Journal of Virology, Vol. 78, Issue 8 https://doi.org/10.1128/JVI.78.8.4363-4369.2004	journal	April 2004
Respiratory Syncytial Virus Nonstructural Proteins NS1 and NS2 Mediate Inhibition of Stat2 Expression and Alpha/Beta Interferon Responsiveness Lo, Mindy S.; Brazas, Robert M.; Holtzman, Michael J. Journal of Virology, Vol. 79, Issue 14 https://doi.org/10.1128/JVI.79.14.9315-9319.2005	journal	July 2005
Effects of Nonstructural Proteins NS1 and NS2 of Human Respiratory Syncytial Virus on Interferon Regulatory Factor 3, NF-κB, and Proinflammatory Cytokines Spann, Kirsten M.; Tran, Kim C.; Collins, Peter L. Journal of Virology, Vol. 79, Issue 9 https://doi.org/10.1128/JVI.79.9.5353-5362.2005	journal	May 2005
Analysis of ATF3, a Transcription Factor Induced by Physiological Stresses and Modulated by gadd153/Chop10 Chen, Benjamin P. C.; Wolfgang, Curt D.; Hai, Tsonwin Molecular and Cellular Biology, Vol. 16, Issue 3 https://doi.org/10.1128/MCB.16.3.1157	journal	March 1996
An Unexpected Encounter: Respiratory Syncytial Virus Nonstructural Protein 1 Interacts with Mediator Subunit MED25 Van Royen, Tessa; Sedeyn, Koen; Moschonas, George D. Journal of Virology, Vol. 96, Issue 19 https://doi.org/10.1128/jvi.01297-22	journal	October 2022
Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population You, Yingjian; Richer, Edward J.; Huang, Tao American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 283, Issue 6 https://doi.org/10.1152/ajplung.00169.2002	journal	December 2002
Bronchial Epithelial Cells Promote the Differentiation of Th2 Lymphocytes in Airway Microenvironment through Jagged/Notch-1 Signaling after RSV Infection Qin, Ling; Qiu, Ke-zi; Hu, Cheng-ping International Archives of Allergy and Immunology, Vol. 179, Issue 1 https://doi.org/10.1159/000495581	journal	January 2019
Rho-Associated Protein Kinase Inhibition Enhances Airway Epithelial Basal-Cell Proliferation and Lentivirus Transduction Horani, Amjad; Nath, Aditya; Wasserman, Mollie G. American Journal of Respiratory Cell and Molecular Biology, Vol. 49, Issue 3 https://doi.org/10.1165/rcmb.2013-0046TE	journal	September 2013
Assemblies of JAG1 and JAG2 determine tracheobronchial cell fate in mucosecretory lung disease Reynolds, Susan D.; Hill, Cynthia L.; Alsudayri, Alfahdah JCI Insight, Vol. 7, Issue 15 https://doi.org/10.1172/jci.insight.157380	journal	August 2022
The common stress responsive transcription factor ATF3 binds genomic sites enriched with p300 and H3K27ac for transcriptional regulation Zhao, Jonathan; Li, Xingyao; Guo, Mingxiong BMC Genomics, Vol. 17, Issue 1 https://doi.org/10.1186/s12864-016-2664-8	journal	May 2016
Peak calling by Sparse Enrichment Analysis for CUT&RUN chromatin profiling Meers, Michael P.; Tenenbaum, Dan; Henikoff, Steven Epigenetics & Chromatin, Vol. 12, Issue 1 https://doi.org/10.1186/s13072-019-0287-4	journal	July 2019
Respiratory Syncytial Virus NS1 Protein Colocalizes with Mitochondrial Antiviral Signaling Protein MAVS following Infection Boyapalle, Sandhya; Wong, Terianne; Garay, Julio PLoS ONE, Vol. 7, Issue 2 https://doi.org/10.1371/journal.pone.0029386	journal	February 2012
Exploitation of the Mediator complex by viruses Rovnak, Joel; Quackenbush, Sandra L. PLOS Pathogens, Vol. 18, Issue 4 https://doi.org/10.1371/journal.ppat.1010422	journal	April 2022
Respiratory Syncytial Virus–Associated Hospitalizations Among Young Children: 2015–2016 Rha, Brian; Curns, Aaron T.; Lively, Joana Y. Pediatrics, Vol. 146, Issue 1 https://doi.org/10.1542/peds.2019-3611	journal	July 2020
Master Regulator Activating Transcription Factor 3 (ATF3) in Metabolic Homeostasis and Cancer Ku, Hui-Chen; Cheng, Ching-Feng Frontiers in Endocrinology, Vol. 11 https://doi.org/10.3389/fendo.2020.00556	journal	August 2020
The Dual Roles of Activating Transcription Factor 3 (ATF3) in Inflammation, Apoptosis, Ferroptosis, and Pathogen Infection Responses Liu, Shuang; Li, Zhangcheng; Lan, Shimei International Journal of Molecular Sciences, Vol. 25, Issue 2 https://doi.org/10.3390/ijms25020824	journal	January 2024
Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling Ban, Junsu; Lee, Na-Rae; Lee, Noh-Jin Viruses, Vol. 10, Issue 12 https://doi.org/10.3390/v10120716	journal	December 2018
Host Responses to Respiratory Syncytial Virus Infection Agac, Ayse; Kolbe, Sophie M.; Ludlow, Martin Viruses, Vol. 15, Issue 10 https://doi.org/10.3390/v15101999	journal	September 2023
ATF3, a Hub of the Cellular Adaptive-Response Network, in the Pathogenesis of Diseases: Is Modulation of Inflammation a Unifying Component? Hai, Tsonwin; Wolford, Christopher C.; Chang, Yi-Seok Gene Expression, Vol. 15, Issue 1 https://doi.org/10.3727/105221610X12819686555015	journal	January 2010
An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites Skene, Peter J.; Henikoff, Steven eLife, Vol. 6 https://doi.org/10.7554/eLife.21856	journal	January 2017
Improved CUT&RUN chromatin profiling tools Meers, Michael P.; Bryson, Terri D.; Henikoff, Jorja G. eLife, Vol. 8 https://doi.org/10.7554/eLife.46314	journal	June 2019
Simple biochemical features underlie transcriptional activation domain diversity and dynamic, fuzzy binding to Mediator Sanborn, Adrian L.; Yeh, Benjamin T.; Feigerle, Jordan T. eLife, Vol. 10 https://doi.org/10.7554/eLife.68068	journal	April 2021