Article
Multidisciplinary Sciences
Xizi Chen, Xinxin Wang, Weida Liu, Yulei Ren, Xuechun Qu, Jiabei Li, Xiaotong Yin, Yanhui Xu
Summary: RNA polymerase II-mediated eukaryotic transcription begins with the assembly of the preinitiation complex (PIC) on core promoters. The +1 nucleosome, positioned about 40 base pairs downstream of the transcription start site (TSS), acts as a barrier to transcription. The study shows that the PIC-Mediator prefers binding to the T40N nucleosome located at the 40 base pairs downstream of the TSS and contacts the T50N nucleosome, but not the T70N nucleosome. The nucleosome facilitates the organization of PIC-Mediator on the promoter and may contribute to transcription initiation. The study reveals the molecular mechanism of PIC-Mediator organization on chromatin and emphasizes the significance of the +1 nucleosome in regulating transcription initiation.
Article
Multidisciplinary Sciences
Sandra Schilbach, Haibo Wang, Christian Dienemann, Patrick Cramer
Summary: This study presents an atomic model for the yeast preinitiation complex (PIC) with core mediator, revealing the molecular details of RNA polymerase II (Pol II) transcription initiation. The structure of the mediator middle module was optimized, and the missing subunit Med1 was identified. The study found that the flexible C-terminal repeat domain (CTD) of Pol II forms defined interactions with the mediator head and middle modules, as well as other regions of the mediator. The binding mode between the yeast mediator and Pol II differs from the human counterpart.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Yanfeng He, Shigeo Sato, Chieri Tomomori-Sato, Shiyuan Chen, Zach H. Goode, Joan W. Conaway, Ronald C. Conaway
Summary: The bZIP transcription factor ATF6 alpha is a master regulator of ER stress response genes, with the multifunctional RNA polymerase II transcription factor Elongin identified as a cofactor for ATF6 alpha-dependent transcription activation. Studies show that Elongin facilitates ATF6 alpha-dependent loading of Mediator at the promoters and enhancers of ER stress response genes, and depletion of Elongin leads to impaired transcription and recruitment of Mediator and its CDK8 kinase subunit during the ER stress response. Overall, these findings reveal a crucial role for Elongin as a loading factor for Mediator in the context of ER stress response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Xizi Chen, Xiaotong Yin, Jiabei Li, Zihan Wu, Yilun Qi, Xinxin Wang, Weida Liu, Yanhui Xu
Summary: This study investigates the mechanisms of TFIID and Mediator proteins in regulating transcription initiation and RNA polymerase activity, revealing their interactions and mutual regulation through structural analysis, as well as the phosphorylation process of Pol II CTD by CDK7.
Article
Cell Biology
Kevin M. Andre, Nathalie Giordanengo Aiach, Veronica Martinez-Fernandez, Leo Zeitler, Adriana Alberti, Arach Goldar, Michel Werner, Cyril Denby Wilkes, Julie Soutourina
Summary: Chromatin organization is crucial for transcriptional regulation. Mediator and RSC contribute to chromatin remodeling and transcriptional regulation by establishing physical contact and coordinating their functions.
Review
Microbiology
Robert Landick
Summary: RNA polymerase plays a crucial role in expressing genetic information through transcription of DNA, and has evolved to sense and process environmental information. Transcriptional pauses, which occur during transcript elongation, play a key role in regulatory decisions. After decades of study, four classes of transcriptional pause signals have been identified, raising numerous questions about how RNA polymerase responds to these signals and the broader regulation of transcript elongation.
ANNUAL REVIEW OF MICROBIOLOGY, VOL 75, 2021
(2021)
Article
Biochemistry & Molecular Biology
Sara Osman, Eusra Mohammad, Michael Lidschreiber, Alexandra Stuetzer, Fanni Laura Bazso, Kerstin C. Maier, Henning Urlaub, Patrick Cramer
Summary: The Cdk8 kinase module (CKM) plays a dual role in gene transcription by regulating mediator function and facilitating transcription initiation. During stress, the kinase activity of Cdk8 is essential for gene activation, suggesting a mechanism for rapid transcriptional response to environmental changes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Plant Sciences
Rekha Agrawal, Fajkus Jiri, Jitendra K. Thakur
Summary: The Mediator complex, which conveys regulatory information from transcription factors to RNA polymerase II, consists of four modules including a kinase module. The kinase module, composed of MED12, MED13, CycC, and CDK8, is able to significantly alter the structure and function of the complex, playing a crucial role in transcription regulation.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Biochemistry & Molecular Biology
Cecile Evrin, Albert Serra-Cardona, Shoufu Duan, Progya P. Mukherjee, Zhiguo Zhang, Karim P. M. Labib
Summary: In eukaryotes, the essential factor Spt5 plays a direct role in the process of re-deposition of nucleosomal histones during transcription. It contains an acidic amino terminal tail called Spt5N, which has a histone-binding motif that is essential for yeast cell viability.
Article
Biochemistry & Molecular Biology
Heqiao Zhang, Dong-Hua Chen, Rayees U. H. Mattoo, David A. Bushnell, Yannan Wang, Chao Yuan, Lin Wang, Chunnian Wang, Ralph E. Davis, Yan Nie, Roger D. Kornberg
Summary: Structural studies of Mediator reveal key amino acid residues and conformational changes that propagate across the entire protein, linking activator- and pol II-interacting regions. The structure provides insight into the role of Mediator as a universal adaptor for transcription control.
Article
Biochemistry & Molecular Biology
Ahmet C. Berkyurek, Giulia Furlan, Lisa Lampersberger, Toni Beltran, Eva-Maria Weick, Emily Nischwitz, Isabela Cunha Navarro, Fabian Braukmann, Alper Akay, Jonathan Price, Falk Butter, Peter Sarkies, Eric A. Miska
Summary: PIWI-interacting RNAs (piRNAs) are small RNAs that regulate germ cell development in animals, and in the nematode Caenorhabditis elegans, the core subunit RPB-9 of RNA polymerase II (RNA Pol II) is identified as essential for piRNA-mediated gene silencing. RPB-9 is required for piRNA biogenesis by recruiting the Integrator complex at piRNA genes for transcriptional termination, suggesting the piRNA pathway has evolved to utilize a mechanism originally used for transcription fidelity.
Article
Multidisciplinary Sciences
Hidefumi Suzuki, Ryota Abe, Miho Shimada, Tomonori Hirose, Hiroko Hirose, Keisuke Noguchi, Yoko Ike, Nanami Yasui, Kazuki Furugori, Yuki Yamaguchi, Atsushi Toyoda, Yutaka Suzuki, Tatsuro Yamamoto, Noriko Saitoh, Shigeo Sato, Chieri Tomomori-Sato, Ronald C. Conaway, Joan W. Conaway, Hidehisa Takahashi
Summary: This study demonstrates the importance of Mediator in the transcription termination of replication-dependent histone genes. Mediator plays a role in pausing RNA polymerase II at the transcript end sites of these genes by associating with Cajal bodies, thereby facilitating the subsequent 3'-end processing.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Liqiang Shen, Giorgio Lai, Linlin You, Jing Shi, Xiaoxian Wu, Maria Puiu, Zhanxi Gu, Yu Feng, Yulia Yuzenkova, Yu Zhang
Summary: This study presents the cryo-EM structures of cyanobacterial transcription initiation complexes, revealing the role of SI3-& sigma; arch interaction in transcription initiation of cyanobacteria. Disruption of this structure affects the growth and stress response of cyanobacteria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Neha Singh, Mohd Asalam, Mohd Owais Ansari, Nadezhda S. Gerasimova, Vasily M. Studitsky, Md Sohail Akhtar
Summary: The epigenetic phenomenon plays a role in the phenotypic variation of organisms by regulating the transcription of protein coding genes. The carboxy terminal domain (CTD) of RNA Polymerase II is thought to bind different protein complexes involved in mRNA biogenesis and export. The epigenetic modifications of CTD mediate its interaction with chromatin and influence histone modifications.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Srinivasan Rengachari, Sandra Schilbach, Shintaro Aibara, Christian Dienemann, Patrick Cramer
Summary: Mediator is a conserved coactivator complex involved in the regulated initiation of transcription at eukaryotic genes. It interacts with transcriptional activators to stimulate RNA polymerase II phosphorylation and promoter escape. The complex structure involves various modules that can affect the activity conformation of CDK7 kinase.
Article
Biochemistry & Molecular Biology
Eric J. Tomko, Olivia Luyties, Jenna K. Rimel, Chi-Lin Tsai, Jill O. Fuss, James Fishburn, Steven Hahn, Susan E. Tsutakawa, Dylan J. Taatjes, Eric A. Galburt
Summary: The general transcription factor TFIIH contains three ATP-dependent catalytic activities and functions in nucleotide excision repair and Pol II transcription initiation. While the functions are conserved between metazoans and yeast, yeast TFIIH drives transcription start-site scanning. Human and yeast core-TFIIH complexes lack processive translocation, with the yeast kinase module aiding in robust transcription start-site scanning.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Olivia Luyties, Dylan J. Taatjes
Summary: The Mediator kinase module plays a crucial role in controlling gene transcription by regulating the activity of transcription factors, elongation of RNA polymerase II, and chromatin structure. It integrates signaling pathways with transcription to enable rapid, stimulus-specific responses and is also associated with human diseases.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Kevin C. Clopper, Dylan J. Taatjes
Summary: This article introduces the development and application of chemical inhibitors associated with transcription and kinases. The authors focus on the function of CDK7, CDK8, CDK9, CDK12, CDK13, and CDK19 kinases and the advantages of inhibitors, and provide strategies and recommendations for experimental analysis.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)