Article
Biochemistry & Molecular Biology
Heankel Lyons, Reshma T. Veettil, Prashant Pradhan, Christy Fornero, Nancy De La Cruz, Keiichi Ito, Mikayla Eppert, Robert G. Roeder, Benjamin R. Sabari
Summary: Components of transcriptional machinery are selectively partitioned into specific condensates, often mediated by protein disorder, to regulate biochemical pathways. In this study, it was found that condensates composed of the intrinsically disordered region (IDR) of MED1 can selectively partition RNA polymerase II and its positive allosteric regulators, while excluding negative regulators. This selective compartmentalization is necessary for gene activation during a cell-state transition and is achieved through alternating blocks of charged amino acids in the IDRs of partitioned proteins.
Article
Genetics & Heredity
Bo-Kuan Wu, Szu-Chieh Mei, Elizabeth H. Chen, Yonggang Zheng, Duojia Pan
Summary: Activation of YAP results in upregulation of TET1, which interacts with TEAD to promote DNA demethylation at YAP target genes in the liver. Loss of TET1 reverses YAP-induced epigenetic and transcriptional changes, and suppresses YAP-induced hepatomegaly and tumorigenesis.
Article
Chemistry, Multidisciplinary
Ruben W. Kolkman, Loes Segerink, Jurriaan Huskens
Summary: By organizing multiple MBDs on a surface, a multivalent binding platform can significantly improve the preselection of hypermethylated DNA from liquid biopsy samples. The selectivity for methylated over non-methylated DNA can be optimized by carefully tuning the MBD density. Implementing such an enrichment step in an analytical process or a lab-on-a-chip device holds strong applicability in a medical setting.
ADVANCED MATERIALS INTERFACES
(2022)
Article
Multidisciplinary Sciences
Nicole DelRosso, Josh Tycko, Peter Suzuki, Cecelia Andrews, Adi Mukund, Ivan Liongson, Connor Ludwig, Kaitlyn Spees, Polly Fordyce, Michael C. Bassik, Lacramioara Bintu
Summary: Human gene expression is regulated by thousands of transcription factors and chromatin regulators. This study systematically measures the activity of over 100,000 protein fragments from these regulators and annotates previously unknown activation and repression domains. The research reveals the necessary residues for activation domain activity and identifies structures or motifs involved in repression. The findings provide valuable insights into the function of transcription factors and chromatin regulators and can aid in gene expression control and predictive modeling of effector domains.
Review
Microbiology
S. Mayo-Perez, Y. Gama-Martinez, S. Davila, N. Rivera, I. Hernandez-Lucas
Summary: This review focuses on the distribution, abundance, evolution, structural organization, transcriptional regulation, and fundamental roles of LysR-type transcriptional regulators (LTTRs) in bacteria, archaea, and algae. It also discusses their involvement in free life, pathogenesis, and bacteria-plant interaction, providing a current understanding of LTTR biology.
CRITICAL REVIEWS IN MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Fei-Man Hsu, Qiu Ya Wu, Emily B. Fabyanic, Alex Wei, Hao Wu, Amander T. Clark
Summary: This study investigates Ten Eleven Translocation 1 (TET1) as a regulator of DNA demethylation and its role in facilitating human primordial germ cell-like cells (hPGCLCs) competency. The findings indicate that 5-hydroxymethylcytosine (5hmC) enriches at specific binding sites in hPGCLCs and is accompanied by localized DNA demethylation. Furthermore, deleting the catalytic domain of TET1 reduces hPGCLC competency, which can be rescued by transitioning hESCs to defined media and a recombinant substrate.
Article
Multidisciplinary Sciences
Jianfang Li, Xinwei Wu, Jie Ke, Minjung Lee, Qingping Lan, Jia Li, Jianxiu Yu, Yun Huang, De-Qiang Sun, Ruiyu Xie
Summary: In this study, the authors demonstrate that TET1 plays a crucial role in the generation of functional insulin-producing cells. They find that FOXA2 physically interacts with TET1 and contributes to the specific recruitment of TET1 to the regulatory elements of pancreatic lineage determinants, mediating chromatin opening.
NATURE COMMUNICATIONS
(2022)
Article
Plant Sciences
Fu-Yu Hung, Yuan-Hsin Shih, Pei-Yu Lin, Yun-Ru Feng, Chenlong Li, Keqiang Wu
Summary: WRKY63 acts as a dual regulator by directly activating FLC under non-vernalization conditions and indirectly repressing FLC during vernalization through inducing COOLAIR and COLDAIR. WRKY63 also activates the expression of COOLAIR and COLDAIR by binding to their promoters. The binding of WRKY63 is associated with increased vernalization-induced gene expression and decreased H3K27me3 levels, indicating its importance in vernalization-induced transcriptional regulation.
Article
Cell Biology
Xin Huang, Nazym Bashkenova, Yantao Hong, Cong Lyu, Diana Guallar, Zhe Hu, Vikas Malik, Dan Li, Hailin Wang, Xiaohua Shen, Hongwei Zhou, Jianlong Wang
Summary: This study uncovers a TET1-PSPC1-Neat1 molecular axis that modulates PRC2 binding affinity to chromatin and bivalent gene transcripts, thereby controlling stem cell bivalency.
Article
Cell Biology
Zhenhua Chen, Keren Zhou, Jianhuang Xue, Andrew Small, Gang Xiao, Le Xuan Truong Nguyen, Zheng Zhang, Emily Prince, Hengyou Weng, Huilin Huang, Zhicong Zhao, Ying Qing, Chao Shen, Wei Li, Li Han, Brandon Tan, Rui Su, Hanjun Qin, Yangchan Li, Dong Wu, Zhaohui Gu, Vu N. Ngo, Xin He, Jianfel Chao, Keith Leung, Kitty Wang, Lei Dong, Xi Qin, Zhenming Cal, Yue Sheng, Yu Chen, Xiwei Wu, Bin Zhang, Yanhong Shi, Guido Marcucci, Zhijian Qian, Mingjiang Xu, Markus Muschen, Jianjun Chen, Xiaolan Deng
Summary: This study reveals that overexpression of TET1 protein plays a crucial oncogenic role in B-ALL independent of its catalytic activity. Targeting the TET1 signaling pathway can effectively decrease B-ALL cell viability and inhibit progression, providing a potential therapeutic strategy for refractory/relapsed B-ALL.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biophysics
Yunxin Deng, Artem K. Efremov, Jie Yan
Summary: Proteins rely on specific interactions with binding partners for their biological functions. Proteins with multiple binding domains can significantly enhance both the binding affinity and specificity, as well as lower the working concentration range. Positive domain-domain cooperativity or the presence of a non-specific binding domain can decrease the working concentration range by increasing the binding affinity without compromising the binding specificity. The configuration of bound ligands shows concentration dependence, providing insights into phase-separation processes in living cells.
BIOPHYSICAL JOURNAL
(2022)
Article
Biology
Sabrina Adam, Julia Bracker, Viviane Klingel, Bernd Osteresch, Nicole E. Radde, Jens Brockmeyer, Pavel Bashtrykov, Albert Jeltsch
Summary: This study reveals that the catalytic activities of TET1 and TET2 are influenced by the flanking sequences of DNA substrates, and this influence is related to 5mC and 5hmC. Furthermore, enhanced flanking sequence preferences and profound effects on the specificity of TET2 are observed at non-CpG sites. The flanking sequence preferences of TET are reflected in genome-wide and local patterns of 5hmC and DNA demethylation.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Maria Arroyo, Florian D. Hastert, Andreas Zhadan, Florian Schelter, Susanne Zimbelmann, Cathia Rausch, Anne K. Ludwig, Thomas Carell, M. Cristina Cardoso
Summary: This study reveals that Tet1 and its short isoform Tet1s have different localization during DNA replication, affecting cytosine modification levels. Tet1s interacts with CRL4(VprBP), ubiquitinated, and recruited to late replicating heterochromatin by Uhrf1, leading to 5-methylcytosine oxidation and chromatin decondensation.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Haizhu Zhang, Zhaoyu Qin, Xuetong Yue, Yang Liu, Xiaogang Sun, Jinwen Feng, Ziyan Xu, Jiangyan Zhao, Kai Li, Jiange Qiu, Wenjun Yang, Fuchu He, Chen Ding
Summary: ATAC-MS is a method to identify transcriptional protein complexes assembled on accessible chromatin, providing insight into the protein machinery in open chromatin. Combined with ATAC-seq, it allows for high-resolution profiling of chromatin-transcriptional machinery. Additionally, the fusion protein ctATAC-MS enables systematic pinpointing of the transcriptional machinery at specific open chromatin regions.
Article
Biochemistry & Molecular Biology
Zhibin Wu, Sizhuo Chen, Mengqi Zhou, Lingbo Jia, Zhenhua Li, Xiyou Zhang, Jinrong Min, Ke Liu
Summary: This study systematically investigates the DNA binding ability of MBDs in Arabidopsis thaliana and finds that only AtMBD6 and AtMBD7 can bind to methylated DNA. Structural analysis reveals the reasons for the weaker binding of AtMBD5 MBD and other AtMBDs to methylated DNA.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Peng Zhang, Cathia Rausch, Florian D. Hastert, Boyana Boneva, Alina Filatova, Sujit J. Patil, Ulrike A. Nuber, Yu Gao, Xinyu Zhao, M. Cristina Cardoso
NUCLEIC ACIDS RESEARCH
(2017)
Article
Genetics & Heredity
Francesco Natale, Annina Scholl, Alexander Rapp, Wei Yu, Cathia Rausch, M. Cristina Cardoso
EPIGENETICS & CHROMATIN
(2018)
Article
Physics, Applied
Anahid Amiri, Florian D. Hastert, Lars-Oliver Heim, Christian Dietz
APPLIED PHYSICS LETTERS
(2020)
Review
Biochemistry & Molecular Biology
Cathia Rausch, Florian D. Hastert, M. Cristina Cardoso
JOURNAL OF MOLECULAR BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Cathia Rausch, Patrick Weber, Paulina Prorok, David Hoerl, Andreas Maiser, Anne Lehmkuhl, Vadim O. Chagin, Corella S. Casas-Delucchi, Heinrich Leonhardt, M. Cristina Cardoso
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Cathia Rausch, Peng Zhang, Corella S. Casas-Delucchi, Julia L. Daiss, Christoph Engel, Gideon Coster, Florian D. Hastert, Patrick Weber, M. Cristina Cardoso
Summary: DNA base modifications, specifically cytosine methylation, have been shown to stabilize the DNA helix and influence genome metabolism. However, oxidation of methylated cytosine can reverse these effects, highlighting the importance of cytosine modifications in regulating DNA helix stability and fine-tuning DNA metabolism locally.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Virology
Marie-Luise Herrlein, Sascha Hein, Tobias Zahn, Ines Mhedhbi, Jan Raupach, Younes Husria, Nuka Ivalu Benz, Jonathan Eisert, Daniela Bender, Vanessa Haberger, Florian D. Hastert, Lisa Henss, Barbara S. Schnierle, Julia C. Stingl, Michael Dreher, Eberhard Hildt
Summary: With the increasing number of vaccinated and convalescent individuals, there is a need for robust methods to quantify neutralizing antibodies. This study compared different neutralization assays using sera from hospitalized COVID-19 patients and found comparable data. The results provide insights into the neutralizing potential of SARS-CoV-2-specific sera.
Article
Virology
Florian D. Hastert, Lisa Henss, Christine von Rhein, Julia Gerbeth, Imke Wieters, Frauke Borgans, Yascha Khodamoradi, Kai Zacharowski, Gernot Rohde, Maria J. G. T. Vehreschild, Barbara S. Schnierle
Summary: This study longitudinally characterized the humoral immune response of 80 COVID-19 patients from the University Hospital Frankfurt/Main, Germany. The results showed that the humoral immune response induced by SARS-CoV-2 infection waned over time, but vaccination increased neutralizing activity against multiple SARS-CoVs, and not against the common cold alpha-coronavirus NL63.
Article
Immunology
Florian D. Hastert, Sascha Hein, Christine von Rhein, Nuka Ivalu Benz, Younes Husria, Doris Oberle, Thorsten J. Maier, Eberhard Hildt, Barbara S. Schnierle
Summary: This study analyzed the immune response to the Omicron variant in individuals vaccinated with different vaccines. The results showed that only individuals vaccinated with mRNA vaccines (such as Comirnaty) or heterologous vaccines (such as AZ/BNT) developed antibody levels with neutralizing capacity against Omicron. Additionally, a third booster vaccination significantly enhanced the immune response to all variants.
Article
Multidisciplinary Sciences
Maria Arroyo, Florian D. Hastert, Andreas Zhadan, Florian Schelter, Susanne Zimbelmann, Cathia Rausch, Anne K. Ludwig, Thomas Carell, M. Cristina Cardoso
Summary: This study reveals that Tet1 and its short isoform Tet1s have different localization during DNA replication, affecting cytosine modification levels. Tet1s interacts with CRL4(VprBP), ubiquitinated, and recruited to late replicating heterochromatin by Uhrf1, leading to 5-methylcytosine oxidation and chromatin decondensation.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Christin Schmidt, Florian D. Hastert, Julia Gerbeth, Tim Beissert, Ugur Sahin, Mario Perkovic, Barbara S. Schnierle
Summary: The study demonstrated that a CHIKV vaccine candidate based on trans-amplifying RNA can induce CHIKV- and RRV-specific immune responses in mice. However, higher antibody titers and neutralization capacity were observed after immunization with a single TR-RNA. There was no significant difference in alphavirus-specific T cell responses between bivalent and single vaccinations.
Article
Chemistry, Multidisciplinary
Anahid Amiri, Florian Hastert, Lukas Stuehn, Christian Dietz
NANOSCALE ADVANCES
(2019)