Article
Multidisciplinary Sciences
Zhenning Wang, Aixia Song, Hao Xu, Shibin Hu, Bolin Tao, Linna Peng, Jingwen Wang, Jiabei Li, Jiali Yu, Li Wang, Ze Li, Xizi Chen, Mengyun Wang, Yayun Chi, Jiong Wu, Yanhui Xu, Hai Zheng, Fei Xavier Chen
Summary: The transcription regulator PAF1 directly affects pausing and elongation during transcription, and also influences the deposition of epigenetic marks it controls. PAF1 degradation leads to the release of polymerase and a decline in histone modifications, which ultimately affects the production of transcriptional outputs.
Article
Biology
James Z. J. Kwan, Thomas F. Nguyen, Anuli C. Uzozie, Marek A. Budzynski, Jieying Cui, Joseph M. C. Lee, Filip Van Petegem, Philipp F. Lange, Sheila S. Teves
Summary: Depletion of TBP in mouse embryonic stem cells does not affect ongoing Pol II transcription, but severely impairs Pol III initiation. However, Pol II transcriptional induction still occurs normally upon TBP depletion. This TBP-independent transcription mechanism is not due to functional redundancy with TRF2, but rather the robustness of the TFIID complex and the Pol II machinery.
Review
Cell Biology
Xuepeng Wang, Yudan Fan, Qiang Wu
Summary: Transcription elongation is a crucial molecular process that regulates gene expression and its malfunction can lead to impaired cellular functions. Understanding the regulatory mechanisms of transcription elongation in embryonic stem cells (ESCs) is important for both basic research and clinical applications in regenerative medicine, as ESCs have the potential to differentiate into various cell types.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Sixian Zhou, Fengli Zhao, Danling Zhu, Qiqi Zhang, Ziwei Dai, Zhe Wu
Summary: This study analyzes the dynamics of Pol II at the 3' ends in Arabidopsis and finds that co-transcriptional splicing regulates Pol II pausing at the 3' end of genes through the number of exons.
Article
Cell Biology
Abderhman Abuhashem, Alexandra G. Chivu, Yixin Zhao, Edward J. Rice, Adam Siepel, Charles G. Danko, Anna-Katerina Hadjantonakis
Summary: This study reveals that RNA Pol II pausing plays a critical role in the pluripotency continuum of mouse embryos. The researchers show that in the absence of NELF, pluripotent stem cells fail to balance the levels of induced and repressed genes and enhancers. Additionally, they find an increase in chromatin-associated NELF during the transition from the naive to later pluripotent states.
GENES & DEVELOPMENT
(2022)
Article
Multidisciplinary Sciences
Bogang Wu, Xiaowen Zhang, Huai-Chin Chiang, Haihui Pan, Bin Yuan, Payal Mitra, Leilei Qi, Hayk Simonyan, Colin N. Young, Eric Yvon, Yanfen Hu, Nu Zhang, Rong Li
Summary: Negative elongation factor B (NELFB) associates with T cell transcription factor TCF1 to regulate CD8 + T cell memory and anti-tumor immune responses. NELF cooperates with TCF1 in T cell responses to cancer by controlling RNA polymerase II pausing and chromatin accessibility at TCF1 target gene loci.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Roberta Dollinger, David S. Gilmour
Summary: Transcription regulation is a tightly coordinated process involving promoter proximal pausing and productive elongation of RNA polymerase II. Advanced techniques and tools have been developed for studying promoter proximal pausing, shedding light on future research directions.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marina Yu Mazina, Elena Kovalenko, Aleksandra A. Evdokimova, Maksim Erokhin, Darya Chetverina, Nadezhda E. Vorobyeva
Summary: This study investigated the recruitment and pausing mechanism of RNA polymerase II during Drosophila metamorphosis. The results indicate that, similar to mid-embryogenesis, promoters are bound by paused RNA polymerase II during metamorphosis, preparing for activation in later developmental stages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Danya J. Martell, Hope E. Merens, Alexis Caulier, Claudia Fiorini, Jacob C. Ulirsch, Robert Ietswaart, Karine Choquet, Giovanna Graziadei, Valentina Brancaleoni, Maria Domenica Cappellini, Caroline Scott, Nigel Roberts, Melanie Proven, Noemi B. A. Roy, Christian Babbs, Douglas R. Higgs, Vijay G. Sankarsn, L. Stirling Churchman
Summary: This study identified mutations in the SUPT5H gene associated with beta-thalassemia, highlighting the importance of RNA polymerase II pausing in erythropoiesis. The disruption of pause release was found to affect cell differentiation and proliferation dynamics, resulting in delayed erythroid-specific gene expression.
DEVELOPMENTAL CELL
(2023)
Article
Biochemistry & Molecular Biology
Guohua Meng, Andrea Lauria, Mara Maldotti, Francesca Anselmi, Isabelle Laurence Polignano, Stefania Rapelli, Daniela Donna, Salvatore Oliviero
Summary: Smad7 functions as a general transcription factor in ESCs, regulating both TGF-beta unrelated genes and key stemness regulators. Loss of Smad7 results in the downregulation of stemness master regulators and the upregulation of developmental genes, leading to loss of the stem phenotype. Integrative analysis reveals that Smad7 co-occupies promoters of highly expressed key stemness regulators by binding to a specific consensus response element.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yousra Yahia, Alexia Pigeot, Amal Zine El Aabidine, Nilay Shah, Nezih Karasu, Ignasi Forne, Stefan Krebs, Helmut Blum, Cyril Esnault, Tom Sexton, Axel Imhof, Dirk Eick, Jean-Christophe Andrau
Summary: This study shows that the largest subunit of RNA polymerase II (Pol II), known as the C-terminal domain (CTD), plays a crucial role in the transcriptional process. Using a CTD-& UDelta;5 mutant in human cells, it was found that this mutant can transcribe genes but has impaired termination. The mutant lacks interaction with the Mediator and Integrator complexes and does not affect the overall genomic organization.
Article
Multidisciplinary Sciences
Vivekanandan Ramalingam, Xinyang Yu, Brian D. Slaughter, Jay R. Unruh, Kaelan J. Brennan, Anastasiia Onyshchenko, Jeffrey J. Lange, Malini Natarajan, Michael Buck, Julia Zeitlinger
Summary: Lola-I, a Drosophila zinc finger transcription factor, can regulate the promoter state independently of gene activation. It makes the target promoters accessible and acquire paused RNA polymerase II throughout the embryo. This promoter transition is crucial for tissue-specific target gene activation. Lola-I mediates this function by depleting promoter nucleosomes.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Mathias Girbig, Juanjuan Xie, Helga Groetsch, Domenico Libri, Odil Porrua, Christoph W. Mueller
Summary: RNA polymerase III terminates transcription by forming a hydrogen-bond network with the poly(dT) region on the non-template strand, as revealed by cryoelectron microscopy. The study also shows that the subcomplex C53-C37 indirectly participates in Pol III termination.
Article
Biology
Ziling Liu, Aiwei Wu, Zhen Wu, Talang Wang, Yixuan Pan, Bing Li, Xumin Zhang, Ming Yu
Summary: The study found that TOX4 is a regulatory factor of PP1 phosphatases and plays an important role in transcriptional regulation. TOX4 can restrict pause release and early elongation but promote late elongation. Loss of TOX4 decreases transcriptional output and may achieve its functions by promoting dephosphorylation of Pol II.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Junaid Akhtar, Yoan Renaud, Steffen Albrecht, Yad Ghavi-Helm, Jean-Yves Roignant, Marion Silies, Guillaume Junion
Summary: m(6)A RNA modification regulates RNAP II pausing in Drosophila cells, affecting pause release, Ser2P occupancy, and nascent RNA transcription. The m(6)A-mediated gene regulation adds another layer to the control of gene expression.
Article
Biology
Nestor Saiz, Laura Mora-Bitria, Shahadat Rahman, Hannah George, Jeremy P. Herder, Jordi Garcia-Ojalvo, Anna-Katerina Hadjantonakis
Biographical-Item
Cell Biology
Ruth M. Arkell, Sally L. Dunwoodie, Anna-Katerina Hadjantonakis, Elizabeth J. Robertson
NATURE CELL BIOLOGY
(2021)
Article
Biology
Sophie M. Morgani, Jie Su, Jennifer Nichols, Joan Massague, Anna-Katerina Hadjantonakis
Summary: Rreb1 is essential for mouse embryonic development, and its loss leads to various defects and embryonic lethality.Understanding the function of Rreb1 in development may provide insights into its role in diseases involving loss of epithelial integrity.
Article
Biology
Sophie M. Morgani, Anna-Katerina Hadjantonakis
Summary: Research reveals that early PGCs in mouse embryos exhibit lower BMP and MAPK responses compared to neighboring cells, while showing similar responses to WNT, indicating distinct signaling regulatory mechanisms between germline and soma cells. Additionally, canonical BMP signaling is not autonomously required for directing PGC-like differentiation.
Article
Biology
Dianne Lumaquin, Eleanor Johns, Emily Montal, Joshua M. Weiss, David Ola, Abderhman Abuhashem, Richard M. White
Summary: The authors developed a lipid droplet transgenic reporter that allows real-time study of lipid droplet dynamics in whole animals and cell cultures. By expressing this transgene in transparent zebrafish and melanoma cells, they discovered the involvement of the nitric oxide pathway in regulating lipid droplets.
Article
Pathology
Bayan Alzumaili, Bin Xu, Maelle Saliba, Abderhman Abuhashem, Ian Ganly, Ronald Ghossein, Nora Katabi
Summary: This study investigates the prognostic features of primary and recurrent pleomorphic adenoma (PA) and finds that age, mitosis, and resection quality are key factors in predicting recurrence.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2022)
Article
Cell Biology
Abderhman Abuhashem, Andrew S. Lee, Alexandra L. Joyner, Anna-Katerina Hadjantonakis
Summary: Targeted protein degradation methods provide a unique approach to study protein function, but their effectiveness in vivo is still unclear. This study tested the functionality of the dTAG degron system in mammalian development and found that it is efficient and non-toxic, with a specific role in early embryo development and zygotic genome activation.
DEVELOPMENTAL CELL
(2022)
Review
Biology
Sayali Chowdhary, Anna-Katerina Hadjantonakis
Summary: The blastocyst is a significant stage in mammalian embryo development, consisting of three cell lineages formed through binary cell fate specification. During this stage, cells differentiate and mature as the embryo implants into the maternal uterus.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Article
Biology
Alexandre Francou, Kathryn Anderson, Anna-Katerina Hadjantonakis
Summary: Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells transform into mesenchymal phenotypes and gain the ability to migrate. This phenomenon is crucial in gastrulation, a highly conserved developmental process. The ingress of epiblast cells at the primitive streak is asynchronous and involves the contraction of apical surfaces through shrinkage of apical junctions. An analysis of apical proteins revealed the enrichment of actomyosin network and Crumbs2 complexes, which may regulate the asynchronous shrinkage of cell junctions. Loss of function experiments demonstrated that Crumbs2 is required for myosin II localization and activity at apical junctions, suggesting its role in actomyosin anisotropy.
Article
Genetics & Heredity
Gilad Barshad, James J. Lewis, Alexandra G. Chivu, Abderhman Abuhashem, Nils Krietenstein, Edward J. Rice, Yitian Ma, Zhong Wang, Oliver J. Rando, Anna-Katerina Hadjantonakis, Charles G. Danko
Summary: By integrating various experimental data, including nucleosome-resolution genomic contact maps, nascent transcription, and perturbations affecting RNA polymerase II dynamics or enhancer activity, this study investigates enhancer-promoter communication. The results demonstrate that functional enhancer-promoter pairs have longer proximity compared to nonfunctional pairs, partly due to factors unrelated to genomic position. Manipulation of transcription cycle reveals the key role of Pol II in enhancer-promoter interactions, with promoter-proximal paused Pol II partially stabilizing these interactions. An updated model is proposed to explain how transcriptional dynamics shape the duration or frequency of enhancer-promoter interactions to facilitate communication.
Article
Cell Biology
Abderhman Abuhashem, Alexandra G. Chivu, Yixin Zhao, Edward J. Rice, Adam Siepel, Charles G. Danko, Anna-Katerina Hadjantonakis
Summary: This study reveals that RNA Pol II pausing plays a critical role in the pluripotency continuum of mouse embryos. The researchers show that in the absence of NELF, pluripotent stem cells fail to balance the levels of induced and repressed genes and enhancers. Additionally, they find an increase in chromatin-associated NELF during the transition from the naive to later pluripotent states.
GENES & DEVELOPMENT
(2022)
Article
Biochemical Research Methods
Abderhman Abuhashem, Anna-Katerina Hadjantonakis
Summary: This article provides a step-by-step protocol for generating genetically engineered mouse models with a degradation tag, enabling the control of degradation of endogenous proteins, which is crucial for studying protein function.
