Article
Biochemistry & Molecular Biology
Can Huang, Xuehui Liu, Yuanyuan Chen, Junshi Zhou, Wenqian Li, Niannian Ding, Li Huang, Jingyu Chen, Zhenfeng Zhang
Summary: This study reports a novel winged helix single-stranded DNA binding protein family called Sul7s, which exhibits an approximately 15-fold higher affinity for single-stranded DNA than for double-stranded DNA in vitro. The solution structure of Sul7s, determined by NMR, reveals a winged helix-turn-helix fold and interacts with single-stranded DNA through a large positively charged binding surface.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Plant Sciences
Fei Gao, Christian Dubos
Summary: Plants tightly control iron uptake, translocation, assimilation, and storage through complex transcriptional regulatory networks, with the bHLH family of transcription factors playing a vital role. Research also involves other classes of transcription factors and post-translational mechanisms. Future research aims to further understand how plants precisely regulate iron homeostasis.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Biochemistry & Molecular Biology
Aparna Boral, Devrani Mitra
Summary: This article focuses on the specific interactions between helix-turn-helix (HTH) transcription factors and substrate DNA molecules, and validates the molecular basis of these interactions through theoretical predictions and experimental studies. The study primarily investigates the heterogeneous interactions between 180 winged-HTH (wHTH) transcription factors and their substrate DNA by constructing a phylogenetic tree, conducting sequence alignment, and analyzing intergroup relationships using network theory. The theoretical investigations, including molecular docking, are successfully tested through experimental characterization of a wHTH transcription factor from Sulfurimonas denitrificans.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Chun-Yi Cho, Patrick H. O'Farrell
Summary: Eukaryotic transcription is initiated by the recruitment of transcription factors (TFs), coactivators, and preinitiation complexes. Live imaging of endogenously tagged proteins in early Drosophila embryos reveals a cascade of events upstream of transcriptional initiation. Sequential and transient recruitment of TFs, coactivators, and RNA polymerase II (RNAPII) occurs in discrete clusters during the activation of non-histone genes. This study suggests that eukaryotic transcription involves a succession of distinct biomolecular condensates, culminating in a self-limiting burst of transcription.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Aileen Julia Riesle, Meijiang Gao, Marcus Rosenblatt, Jacques Hermes, Helge Hass, Anna Gebhard, Marina Veil, Bjorn Gruening, Jens Timmer, Daria Onichtchouk
Summary: This study investigates the combinatorial mechanisms of genome activation and shows that zebrafish genome activators Pou5f3 and Nanog exhibit different roles in the activation process. They act as pioneer-like transcription factors on synergistic enhancers, promoting histone acetylation and transcription activation. However, on antagonistic enhancers, one of the factors acts as a non-pioneer-like transcription factor, competing with the activator and blocking its effects. This activator-blocker mechanism restricts widespread transcriptional activation and prevents premature expression of late developmental genes in early embryos.
NATURE COMMUNICATIONS
(2023)
Review
Immunology
Eva Neugebauer, Aura M. Bastidas-Quintero, Daniel Weidl, Florian Full
Summary: This article reviews the current research progress on how viruses utilize pioneer factors for viral replication and persistence in the host, as well as for the development of viral cancer.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Plant Sciences
Eun-Deok Kim, Keiko U. Torii
Summary: The formation of stomata is a significant model system for understanding stem cell fate commitment. The regulatory strategies governing cell fate commitment differ between embryonic and postembryonic stomatal development. The interplay of transcription factors and cell cycle machineries is crucial for cell differentiation. Recent studies have provided insights into the molecular mechanisms underlying the interaction between transcription factors and epigenetic machineries.
PLANT CELL AND ENVIRONMENT
(2023)
Review
Cell Biology
Brittany Cain, Brian Gebelein
Summary: Metazoans express multiple Hox transcription factors to specify cell fate along the anterior-posterior axis. Understanding how Hox factors regulate target genes for morphogenesis poses challenges on distinguishing their roles in activating/repressing genes for distinct segment identities and impacting organ development in a cell type-specific manner. Recent studies suggest Hox factors modify gene chromatin and utilize interactions with co-activators and co-repressors for accurate transcriptional outcomes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Eleanor Elise Paul, Assen Marintchev
Summary: The HEAT and PCI domains are two related domain families, but the PCI domains may be a subset of the HEAT domain family. The PCI domains have structural similarity with the HEAT domains due to the acquisition of the WH subdomain.
Article
Biochemistry & Molecular Biology
Rupesh Kumar, Maged Mostafa Mahmoud, Hanaa M. Tashkandi, Shafiul Haque, Steve Harakeh, Kalaiarasan Ponnusamy, Shazia Haider
Summary: This study aimed to identify key molecules in colorectal cancer using a computational systems biology approach. A protein-protein interaction network was constructed, and TP53, CTNBB1, AKT1, EGFR, HRAS, JUN, RHOA, and EGF were identified as key molecules. Regulatory networks of these key molecules were also constructed, revealing important regulatory factors. Biochemical investigation of these key regulators could provide further understanding of their role in the pathophysiology of colorectal cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Chuhui Wang, Xueqing Zong, Fanjie Wu, Ricky Wai Tak Leung, Yaohua Hu, Jing Qin
Summary: This study identified 118 DRBPs that function as both transcription factors and splicing factors. By analyzing various experimental data, a two-layer regulatory network system centered on four DRBP-SFs was discovered, proposing potential regulatory models in chronic myeloid leukemia (CML). This research provides new insights into the mechanisms of DRBPs and regulatory networks, with implications for understanding the development of CML.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Medicinal
Burcu Ozden, Ramachandran Boopathi, Ayse Bercin Barlas, Imtiaz N. Lone, Jan Bednar, Carlo Petosa, Seyit Kale, Ali Hamiche, Dimitar Angelov, Stefan Dimitrov, Ezgi Karaca
Summary: This work dissects the binding mode of Sox Pioneer Transcription Factors (PTFs) by combining molecular simulations and physiochemistry approaches. The results show that Sox can bind to compact nucleosomes without causing significant conformational changes when the consensus DNA is located on the solvent-facing DNA strand. The study also reveals that both base-specific interactions and Sox-induced DNA changes are required for sequence-specific nucleosomal DNA recognition.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Naoki Watanabe, Masaki Nakano, Yachiyo Mitsuishi, Norikazu Hara, Tatsuo Mano, Atsushi Iwata, Shigeo Murayama, Toshiharu Suzuki, Takeshi Ikeuchi, Masaki Nishimura
Summary: The study revealed that the downregulation of FAM3C in the AD brain may be a risk factor for A beta accumulation and eventually AD development. Transcriptional mechanisms involving SP1, EBF1, SMAD1, and KLF6 were identified as factors influencing the expression of FAM3C, with reduced nuclear levels of SP1 and EBF1 in AD brains contributing to the observed transcriptional downregulation.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biophysics
Anupam Mondal, Sujeet Kumar Mishra, Arnab Bhattacherjee
Summary: A discrete-state stochastic model has been proposed to study the search mechanism of pioneer factors on nucleosomal DNA, showing a fine balance between nucleosome association and dissociation rates to minimize search time. This differs from the speed-stability paradox of protein target search on naked DNA, providing a plausible framework for understanding the search process on nucleosomal DNA by pioneer factors.
BIOPHYSICAL JOURNAL
(2021)
Review
Cell Biology
Mona Teng, Stanley Zhou, Changmeng Cai, Mathieu Lupien, Housheng Hansen He
Summary: Prostate cancer, the most commonly diagnosed non-cutaneous cancer in North American men, is often treated with androgen deprivation therapy. However, resistance can develop, leading to lethal disease. FOXA1, a pioneer factor that helps shape and regulate androgen receptor signaling, plays a crucial role in prostate cancer development and progression. Mutations in FOXA1 can result in functional alterations, and post-translational modifications can also modulate its activity in prostate cancer. Identifying the function and regulation of FOXA1 in prostate cancer is important for guiding future clinical interventions.
Review
Genetics & Heredity
Elisabetta Manduchi, Joseph D. Romano, Jason H. Moore
Summary: Parametric statistical methods have traditionally been used in genetic analysis of complex traits, but machine learning methods are better suited for detecting and modeling patterns in complex genetic architectures. The goal of AutoML is to eliminate guesswork by automatically identifying the right algorithms and hyperparameters for optimization. This review discusses the promises and challenges of AutoML in genetic analysis and emphasizes the potential for developing novel AutoML methods and software in the field of genetics and genomics.
Article
Endocrinology & Metabolism
Beatriz Merino, Elena Casanueva-Alvarez, Ivan Quesada, Carlos M. Gonzalez-Casimiro, Cristina M. Fernandez-Diaz, Tamara Postigo-Casado, Malcolm A. Leissring, Klaus H. Kaestner, German Perdomo, Irene Cozar-Castellano
Summary: This study found that loss of IDE function in alpha cells leads to impaired alpha cell function, resulting in abnormal glucagon secretion and hyperglucagonaemia. The study also revealed that IDE deficiency in alpha cells impairs the ability to suppress glucagon release in the presence of high glucose or insulin, and contributes to alpha-synuclein aggregation which may affect glucagon secretion via cytoskeletal dysfunction.
Article
Mathematical & Computational Biology
Roland Albert A. Romero, Mariefel Nicole Y. Deypalan, Suchit Mehrotra, John Titus Jungao, Natalie E. Sheils, Elisabetta Manduchi, Jason H. Moore
Summary: This study aims to ascertain and compare the performances of Automated Machine Learning (AutoML) tools on large, highly imbalanced healthcare datasets. The results show that the AutoML tools did not differ significantly from each other and all models performed poorly in predicting disease outcomes. The study provides a specific use-case to illustrate the selection of an optimal prediction threshold and highlights the challenges of healthcare datasets for AutoML tools.
Article
Genetics & Heredity
Patricia Caetano Mota, Miguel Luz Soares, Carlos Daniel Vasconcelos, Antonio Carlos Ferreira, Bruno A. Lima, Elisabetta Manduchi, Jason H. Moore, Natalia Melo, Helder Novais-Bastos, Jose Miguel Pereira, Susana Guimaraes, Conceicao Souto Moura, Jose Agostinho Marques, Antonio Morais
Summary: In this study, the association between idiopathic pulmonary fibrosis (IPF) and single-nucleotide polymorphisms (SNPs) of certain candidate genes was investigated. The MUC5B rs35705950 SNP was found to be significantly associated with IPF susceptibility, while the MUC5B-TOLLIP T-C-T-C haplotype was associated with improved survival in IPF patients. These findings could be valuable for prognosis and stratification of IPF patients.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Review
Cell Biology
Melissa M. M. Rowe, Klaus H. H. Kaestner
Summary: Non-coding RNAs (ncRNAs) play important roles in liver disease and regeneration. This review focuses on key microRNAs (miRs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in the liver. Specifically, it highlights the role of miR-122, miR-21, the let-7 family of miRs, miR-451a, miR-144, and MALAT1.
Article
Gastroenterology & Hepatology
Hannah M. Kolev, Avital Swisa, Elisabetta Manduchi, Yemin Lan, Rachel R. Stine, Giuseppe Testa, Klaus H. Kaestner
Summary: This study investigated the role of H3K27me3 demethylation in the intestine and found that the demethylases KDM6A/B are required for the full transcriptomic and epigenomic landscape of the intestinal epithelium and the expression of key Paneth cell genes.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Psychiatry
Darrell Eacret, Elisabetta Manduchi, Julia Noreck, Emma Tyner, Polina Fenik, Amelia D. Dunn, Jonathan Schug, Sigrid C. Veasey, Julie A. Blendy
Summary: Disrupted sleep is a common symptom in psychiatric disorders, including substance use disorders. This study focuses on the impact of morphine, an opioid drug, on sleep. The researchers found that chronic morphine exposure significantly disrupts sleep, particularly during the dark cycle, and this effect is associated with increased neural activity in the Paraventricular Nucleus of the Thalamus (PVT). This suggests that PVT neurons expressing Mu Opioid Receptors (MORs) play an important role in mediating morphine-induced sleep disturbance.
TRANSLATIONAL PSYCHIATRY
(2023)
Letter
Oncology
Jinping Liu, Lan Cheng, Hilana El-Mekkoussi, Charles-Antoine Assenmacher, Michelle Y. Y. Lee, Danielle R. Jaffe, Kaisha Garvin-Darby, Ashleigh Morgan, Elisabetta Manduchi, Jonathan Schug, Klaus H. Kaestner
CANCER COMMUNICATIONS
(2023)
Letter
Endocrinology & Metabolism
Abhijeet R. Patil, Jonathan Schug, Ali Naji, Klaus H. Kaestner, Robert B. Faryabi, Golnaz Vahedi
Article
Oncology
Apexa Modi, Gonzalo Lopez, Karina L. Conkrite, Chun Su, Tsz Ching Leung, Sathvik Ramanan, Elisabetta Manduchi, Matthew E. Johnson, Daphne Cheung, Samantha Gadd, Jinghui Zhang, Malcolm A. Smith, Jaime M. Guidry Auvil, Soheil Meshinchi, Elizabeth J. Perlman, Stephen P. Hunger, John M. Maris, Andrew D. Wells, Struan F. A. Grant, Sharon J. Diskin
Summary: This study curated and analyzed RNA sequencing data for 1,044 pediatric leukemia and solid tumors, revealing stable expression of lncRNAs in six pediatric cancers and their association with key processes such as proliferation, metabolism, and DNA damage. By integrating various analyses, several lncRNAs were prioritized for experimental validation.
Correction
Endocrinology & Metabolism
Beatriz Merino, Elena Casanueva-Alvarez, Ivan Quesada, Carlos M. Gonzalez-Casimiro, Cristina M. Fernandez-Diaz, Tamara Postigo-Casado, Malcolm A. Leissring, Klaus H. Kaestner, German Perdomo, Irene Cozar-Castellano
Review
Gastroenterology & Hepatology
Hannah M. Kolev, Klaus H. Kaestner
Summary: This article introduces the fascinating process of mammalian intestinal development, from its earliest origins to a complex organ system. It explains the key signaling molecules and cell types involved in this process.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Medicine, Research & Experimental
Nicolai M. Doliba, Andrea V. Rozo, Jeffrey Roman, Wei Qin, Daniel Traum, Long Gao, Jinping Liu, Elisabetta Manduchi, Chengyang Liu, Maria L. Golson, Golnaz Vahedi, Ali Naji, Franz M. Matschinsky, Mark A. Atkinson, Alvin C. Powers, Marcela Brissova, Klaus H. Kaestner, Doris A. Stoffers
Summary: This study found that alpha cell dysfunction exists during the early stages of GADA(+) state, even when alpha cell mass is still normal. This has important implications for understanding the role of early alpha cell dysfunction in the progression of T1D.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemical Research Methods
Elisabetta Manduchi, Trang T. Le, Weixuan Fu, Jason H. Moore
Summary: Machine Learning approaches, such as TPOT, are being increasingly used in biomedical applications. This study aimed to assess the suitability of TPOT in genomics and identify SNP combinations associated with coronary artery disease (CAD). The results showed a promising approach towards precision medicine.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2022)
