Catherine Cifuentes-Rojas
Harvard University
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Publication
Featured researches published by Catherine Cifuentes-Rojas.
Molecular Cell | 2014
Catherine Cifuentes-Rojas; Alfredo Hernandez; Kavitha Sarma; Jeannie T. Lee
Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that is localized to thousands of mammalian genes. Though important to human disease and as a drug target, how PRC2 is recruited remains unclear. One model invokes cis-regulatory RNA. Herein, we biochemically and functionally probe PRC2s recognition of RNA using the X-inactivation model. We observe surprisingly high discriminatory capabilities. While SUZ12 and JARID2 subunits can bind RNA, EZH2 has highest affinity and is somewhat promiscuous. EED regulates the affinity of EZH2 for RNA, lending greater specificity to PRC2-RNA interactions. Intriguingly, while RNA is crucial for targeting, RNA inhibits EZH2s catalytic activity. JARID2 weakens PRC2s binding to RNA and relieves catalytic inhibition. We propose that RNA guides PRC2 to its target but inhibits its enzymatic activity until PRC2 associates with JARID2 on chromatin. Our study provides a molecular view of regulatory interactions between RNA and PRC2 at the chromatin interface.
Molecular Cell | 2015
Chen Davidovich; Xueyin Wang; Catherine Cifuentes-Rojas; Karen J. Goodrich; Anne R. Gooding; Jeannie T. Lee; Thomas R. Cech
Polycomb repressive complex-2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Early works suggested binding specificity of PRC2 to certain long non-coding RNAs for recruitment to chromatin. More recent studies provided evidence both in favor and against this idea. Here, we bridge the two existing models of PRC2-RNA interaction. RepA RNA is a good binding partner for PRC2, while multiple non-relevant RNAs, including bacterial mRNAs, also bind PRC2; Kds depend to some extent on the experimental conditions. Human and mouse PRC2 have broadly similar RNA-binding properties in vitro. Examination of evidence supporting an existing model for site-specific recruitment of PRC2 by a well-defined RNA motif in cells reveals that results are PRC2 independent. We conclude that promiscuous and specific RNA-binding activities of PRC2 in vitro are not mutually exclusive, and that binding specificity in vivo remains to be demonstrated.
Molecular & Cellular Proteomics | 2015
Verena K. Maier; Caitlin M. Feeney; Jordan E. Taylor; Amanda L. Creech; Jana W. Qiao; Attila Szanto; Partha P. Das; Nicholas Chevrier; Catherine Cifuentes-Rojas; Stuart H. Orkin; Steven A. Carr; Jacob D. Jaffe; Philipp Mertins; Jeannie T. Lee
Cell-type specific gene silencing by histone H3 lysine 27 and lysine 9 methyltransferase complexes PRC2 and G9A-GLP is crucial both during development and to maintain cell identity. Although studying their interaction partners has yielded valuable insight into their functions, how these factors are regulated on a network level remains incompletely understood. Here, we present a new approach that combines quantitative interaction proteomics with global chromatin profiling to functionally characterize repressive chromatin modifying protein complexes in embryonic stem cells. We define binding stoichiometries of 9 new and 12 known interaction partners of PRC2 and 10 known and 29 new interaction partners of G9A-GLP, respectively. We demonstrate that PRC2 and G9A-GLP interact physically and share several interaction partners, including the zinc finger proteins ZNF518A and ZNF518B. Using global chromatin profiling by targeted mass spectrometry, we discover that even sub-stoichiometric binding partners such as ZNF518B can positively regulate global H3K9me2 levels. Biochemical analysis reveals that ZNF518B directly interacts with EZH2 and G9A. Our systematic analysis suggests that ZNF518B may mediate the structural association between PRC2 and G9A-GLP histone methyltransferases and additionally regulates the activity of G9A-GLP.
Molecular & Cellular Proteomics | 2015
Verena K. Maier; Caitlin M. Feeney; Jordan E. Taylor; Amanda L. Creech; Jana W. Qiao; Attila Szanto; Partha P. Das; Nicholas Chevrier; Catherine Cifuentes-Rojas; Stuart H. Orkin; Steven A. Carr; Jacob D. Jaffe; Philipp Mertins; Jeannie T. Lee
Cell-type specific gene silencing by histone H3 lysine 27 and lysine 9 methyltransferase complexes PRC2 and G9A-GLP is crucial both during development and to maintain cell identity. Although studying their interaction partners has yielded valuable insight into their functions, how these factors are regulated on a network level remains incompletely understood. Here, we present a new approach that combines quantitative interaction proteomics with global chromatin profiling to functionally characterize repressive chromatin modifying protein complexes in embryonic stem cells. We define binding stoichiometries of 9 new and 12 known interaction partners of PRC2 and 10 known and 29 new interaction partners of G9A-GLP, respectively. We demonstrate that PRC2 and G9A-GLP interact physically and share several interaction partners, including the zinc finger proteins ZNF518A and ZNF518B. Using global chromatin profiling by targeted mass spectrometry, we discover that even sub-stoichiometric binding partners such as ZNF518B can positively regulate global H3K9me2 levels. Biochemical analysis reveals that ZNF518B directly interacts with EZH2 and G9A. Our systematic analysis suggests that ZNF518B may mediate the structural association between PRC2 and G9A-GLP histone methyltransferases and additionally regulates the activity of G9A-GLP.
Molecular & Cellular Proteomics | 2015
Verena K. Maier; Caitlin M. Feeney; Jordan E. Taylor; Amanda L. Creech; Jana W. Qiao; Attila Szanto; Partha P. Das; Nicholas Chevrier; Catherine Cifuentes-Rojas; Stuart H. Orkin; Steven A. Carr; Jacob D. Jaffe; Philipp Mertins; Jeannie T. Lee
Cell-type specific gene silencing by histone H3 lysine 27 and lysine 9 methyltransferase complexes PRC2 and G9A-GLP is crucial both during development and to maintain cell identity. Although studying their interaction partners has yielded valuable insight into their functions, how these factors are regulated on a network level remains incompletely understood. Here, we present a new approach that combines quantitative interaction proteomics with global chromatin profiling to functionally characterize repressive chromatin modifying protein complexes in embryonic stem cells. We define binding stoichiometries of 9 new and 12 known interaction partners of PRC2 and 10 known and 29 new interaction partners of G9A-GLP, respectively. We demonstrate that PRC2 and G9A-GLP interact physically and share several interaction partners, including the zinc finger proteins ZNF518A and ZNF518B. Using global chromatin profiling by targeted mass spectrometry, we discover that even sub-stoichiometric binding partners such as ZNF518B can positively regulate global H3K9me2 levels. Biochemical analysis reveals that ZNF518B directly interacts with EZH2 and G9A. Our systematic analysis suggests that ZNF518B may mediate the structural association between PRC2 and G9A-GLP histone methyltransferases and additionally regulates the activity of G9A-GLP.
Molecular Cell | 2015
Johnny T. Kung; Barry Kesner; Jee Young An; Janice Y. Ahn; Catherine Cifuentes-Rojas; David Colognori; Yesu Jeon; Attila Szanto; Brian C. Del Rosario; Stefan F. Pinter; Jennifer A. Erwin; Jeannie T. Lee
Cell | 2017
Hsueh-Ping Chu; Catherine Cifuentes-Rojas; Barry Kesner; Eric Aeby; Hun-goo Lee; Chunyao Wei; Hyun Jung Oh; Myriam Boukhali; Wilhelm Haas; Jeannie T. Lee
Cell | 2016
Athanasios Zovoilis; Catherine Cifuentes-Rojas; Hsueh-Ping Chu; Alfredo Hernandez; Jeannie T. Lee
The FASEB Journal | 2015
Jeannie T. Lee; Kavitha Sarma; Catherine Cifuentes-Rojas; Ayla Ergun; Amanda M. Del Rosario; Yesu Jeon; Forest M. White; Ruslan I. Sadreyev
PMC | 2014
Kavitha Sarma; Catherine Cifuentes-Rojas; Ayla Ergun; Yesu Jeon; Ruslan I. Sadreyev; Jeannie T. Lee; Amanda M. Del Rosario; Forest M. White