Article
Multidisciplinary Sciences
Jiejie Zhang, Chen C. Li, Xin Li, Yaxi Liu, Qianhao Wang, Guangyu Zhang, Haiqing Xiong, Aibin He, Shanshan Ai
Summary: Distinct enhancer elements can regulate the cell type-specific expression of the developmental gene. We comprehensively studied enhancers U1 and U2 in controlling Nkx2-5 transcription during heart development. Our findings suggest that U1 and U2 have redundant functions at early stages, but U2 instead of U1 supports Nkx2-5 expression at later stages. Deletions of both enhancers result in reduced Nkx2-5 dosage and disturbed enhancer landscape in mouse hearts.
Article
Multidisciplinary Sciences
Mengyi Song, Xuefei Yuan, Claudia Racioppi, Meaghan Leslie, Nathan Stutt, Anastasiia Aleksandrova, Lionel Christiaen, Michael D. Wilson, Ian C. Scott
Summary: GATA4/5/6 transcription factors are crucial for heart development and regulate the transition from mesoderm to cardiac fate. Loss of Gata5/6 alters the population structure of mesendoderm-derived cells and leads to extensive changes in chromatin accessibility near cardiac and pharyngeal genes.
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)
Article
Multidisciplinary Sciences
Wenyu Hu, Anqi Dong, Kohei Karasaki, Shota Sogabe, Daiki Okamoto, Masato Saigo, Mari Ishida, Masao Yoshizumi, Hiroki Kokubo
Summary: Smad4 plays an essential role in cardiomyocyte differentiation by controlling both transcription and the nuclear localization of Nkx2-5.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Zengde Chi, Yan Lu, Yinlong Yang, Bingqing Li, Peiyuan Lu
Summary: PD-1 serves as a crucial co-inhibitory receptor in regulating T cell immunity and peripheral tolerance. It plays a dual role in preventing T cell overactivation and maintaining T cell exhaustion. Additionally, the PD-1 signaling pathway is exploited by tumor cells to evade immune responses and is essential for maintaining peripheral tolerance and preventing autoimmune diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Nozomu Takata, Jason M. Miska, Marc A. Morgan, Priyam Patel, Leah K. Billingham, Neha Joshi, Matthew J. Schipma, Zachary J. Dumar, Nikita R. Joshi, Alexander V. Misharin, Ryan B. Embry, Luciano Fiore, Peng Gao, Lauren P. Diebold, Gregory S. McElroy, Ali Shilatifard, Navdeep S. Chandel, Guillermo Oliver
Summary: Using eye organoids and mouse models, the authors demonstrate that lactate plays a bioenergetic independent role as a cell signaling molecule during early eye formation in mice. The study reveals the importance of aerobic glycolysis in retinal development and identifies specific glucose transporters and glycolytic genes involved. Lactate-mediated upregulation of eye-field transcription factors is controlled by epigenetic modifications.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yuzhou Wang, Yu Zhang, Ning Yu, Bingyan Li, Jiazhen Gong, Yide Mei, Jianqiang Bao, Shisong Ma
Summary: Researchers developed a universal human gene expression predictor called EXPLICIT-Human and used it to decode transcriptional regulation. The predictor accurately reconstructed transcriptomes for a wide range of tissues and conditions using the expression of 1613 transcription factors. It extracted significant interacting TF-target gene pairs, enabling inference of TF regulators for various pathways. The method showed better performance in recovering the correct TF regulators compared to existing tools.
JOURNAL OF GENETICS AND GENOMICS
(2023)
Article
Cardiac & Cardiovascular Systems
Pingzhu Zhou, Yan Zhang, Isha Sethi, Lincai Ye, Michael A. Trembley, Yangpo Cao, Brynn N. Akerberg, Feng Xiao, Xiaoran Zhang, Kai Li, Blake D. Jardin, Neil Mazumdar, Qing Ma, Aibin He, Bin Zhou, William T. Pu
Summary: This study investigated the chromatin occupancy of GATA4 during heart development. The researchers found that GATA4 occupies genomic regions with lineage-specific enhancers in cardiomyocyte and endocardial lineages. They also discovered that non-pioneer transcription factors NKX2-5 and ETS1 guide the activity of GATA4, promoting its binding and opening of chromatin, and regulating endocardial development.
CIRCULATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ewelina Szczepanek-Parulska, Bartlomiej Budny, Martyna Borowczyk, Igor Zhukov, Kosma Szutkowski, Katarzyna Zawadzka, Raiha Tahir, Andrzej Minczykowski, Marek Niedziela, Marek Ruchala
Summary: This study identified a rare variant in the NKX2-5 gene in two siblings with thyroid hemiagenesis, providing evidence for its potential contribution to the pathogenesis of this condition. However, further research is needed to determine the impact of other factors on the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Kevin Rychel, Katherine Decker, Anand Sastry, Patrick Phaneuf, Saugat Poudel, Bernhard O. Palsson
Summary: iModulonDB is a knowledgebase of prokaryotic transcriptional regulation computed from high-quality transcriptomic datasets using Independent Component Analysis (ICA). Users can select an organism, search or browse curated iModulons, and access interactive dashboards with plots and tables for each iModulon and gene. This site enhances research by providing scientists with co-expressed gene sets and their activities, improving understanding of regulator-gene relationships and facilitating the discovery of transcription factors.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Joshua E. Burda, Timothy M. O'Shea, Yan Ao, Keshav B. Suresh, Shinong Wang, Alexander M. Bernstein, Ashu Chandra, Sandeep Deverasetty, Riki Kawaguchi, Jae H. Kim, Sarah McCallum, Alexandra Rogers, Shalaka Wahane, Michael Sofroniew
Summary: This study reveals the regulatory mechanism of genes associated with astrocyte reactivity through biological and informatic analyses. These genes show heterogeneity across different central nervous system disorders and are regulated by transcriptional regulators. By modulating reactivity, these transcriptional regulators can alter the outcome of the disorders and may serve as therapeutic targets.
Article
Biochemical Research Methods
Mark Jayson Cortez, Hyukpyo Hong, Boseung Choi, Jae Kyoung Kim, Kresimir Josic
Summary: This study proposes a non-Markovian, hierarchical Bayesian inference framework for quantifying the variability of cellular processes within and across cells in a population. By using a delayed birth-death process, the proposed hierarchical framework is shown to be robust and leads to improved estimates compared to its non-hierarchical counterpart when applied to in silico and experimental data. The mean delays in protein production are reported to be larger than previously thought, with a coefficient of variation of around 0.2 across the population, and not strongly correlated with protein production or growth rates.
Article
Biochemistry & Molecular Biology
Evan M. Cofer, Joao Raimundo, Alicja Tadych, Yuji Yamazaki, Aaron K. Wong, Chandra L. Theesfeld, Michael S. Levine, Olga G. Troyanskaya
Summary: DeepArk is a set of deep learning models for model species, accurately predicting various context-specific regulatory features and enabling the prediction of regulatory impact of genomic variants, even rare or previously unobserved ones, as well as facilitating regulatory annotation of understudied model species through in vivo studies.
Article
Immunology
Noam Kadouri, Tal Givony, Shir Nevo, Joschka Hey, Shifra Ben Dor, Golda Damari, Bareket Dassa, Jan Dobes, Dieter Weichenhan, Marion Bahr, Michelle Paulsen, Rebecca Haffner-Krausz, Marcus A. Mall, Christoph Plass, Yael Goldfarb, Jakub Abramson
Summary: This study reveals the importance of FOXN1 in the development of thymic epithelial cells and hair follicle cells, and identifies key regulatory regions and transcription factors involved in its expression.
SCIENCE IMMUNOLOGY
(2022)
Review
Plant Sciences
William Agbemafle, Min May Wong, Diane C. Bassham
Summary: This review summarizes key regulatory mechanisms for modulating autophagy through post-translational modification or transcriptional regulation. Plants activate cellular responses to adapt to changing environmental conditions, one of which is autophagy, where cellular components are delivered to the vacuole for degradation. Autophagy is activated by various conditions, and the pathways controlling its activation are being elucidated. However, there is still much to discover regarding how these factors work together to properly modulate autophagy in response to specific signals.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Article
Biochemistry & Molecular Biology
Matthew J. Brody, Tobias G. Schips, Davy Vanhoutte, Onur Kanisicak, Jason Karch, Bryan D. Maliken, N. Scott Blair, Michelle A. Sargent, Vikram Prasad, Jeffery D. Molkentin
MOLECULAR AND CELLULAR BIOLOGY
(2016)
Article
Cardiac & Cardiovascular Systems
Matthew J. Brody, Li Feng, Adrian C. Grimes, Timothy A. Hacker, Timothy M. Olson, Timothy J. Kamp, Ravi C. Balijepalli, Youngsook Lee
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2016)
Article
Multidisciplinary Sciences
Onur Kanisicak, Hadi Khalil, Malina J. Ivey, Jason Karch, Bryan D. Maliken, Robert N. Correll, Matthew J. Brody, Suh-Chin J. Lin, Bruce J. Aronow, Michelle D. Tallquist, Jeffery D. Molkentin
NATURE COMMUNICATIONS
(2016)
Article
Biology
Davy Vanhoutte, Tobias G. Schips, Jennifer Q. Kwong, Jennifer Davis, Andoria Tjondrokoesoemo, Matthew J. Brody, Michelle A. Sargent, Onur Kanisicak, Hong Yi, Quan Q. Gao, Joseph E. Rabinowitz, Talila Volk, Elizabeth M. McNally, Jeffery D. Molkentin
Article
Physiology
Matthew J. Brody, Youngsook Lee
FRONTIERS IN PHYSIOLOGY
(2016)
Article
Biology
Jason Karch, Tobias G. Schips, Bryan D. Maliken, Matthew J. Brody, Michelle A. Sargent, Onur Kanisciak, Jeffery D. Molkentin
Article
Biochemistry & Molecular Biology
Matthew J. Brody, Davy Vanhoutte, Tobias G. Schips, Justin G. Boyer, Chinmay V. Bakshi, Michelle A. Sargent, Allen J. York, Jeffery D. Molkentin
MOLECULAR AND CELLULAR BIOLOGY
(2018)
Article
Multidisciplinary Sciences
Jason Karch, Onur Kanisicak, Matthew J. Brody, Michelle A. Sargent, Demetria M. Michael, Jeffery D. Molkentin
Article
Multidisciplinary Sciences
Tobias G. Schips, Davy Vanhoutte, Alexander Vo, Robert N. Correll, Matthew J. Brody, Hadi Khalil, Jason Karch, Andoria Tjondrokoesoemo, Michelle A. Sargent, Marjorie Maillet, Robert S. Ross, Jeffery D. Molkentin
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Matthew J. Brody, Davy Vanhoutte, Chinmay V. Bakshi, Ruije Liu, Robert N. Correll, Michelle A. Sargent, Jeffery D. Molkentin
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Review
Physiology
Kobina Essandoh, Julie M. Philippe, Paul M. Jenkins, Matthew J. Brody
FRONTIERS IN PHYSIOLOGY
(2020)
Review
Biochemistry & Molecular Biology
James P. Teuber, Kobina Essandoh, Scott L. Hummel, Nageswara R. Madamanchi, Matthew J. Brody
Summary: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases play crucial roles in regulating oxidative stress, redox signaling, and the development of heart failure with preserved ejection fraction (HFpEF). HFpEF is associated with various systemic pathologies and multiple organ dysfunctions. NOX enzymes are involved in diastolic function and several HFpEF-associated comorbidities in animal models.
Article
Cardiac & Cardiovascular Systems
Kobina Essandoh, Arasakumar Subramani, Olivia A. Ferro, James P. Teuber, Sribharat Koripella, Matthew J. Brody
Summary: Production and release of natriuretic peptides by the stressed heart can reduce cardiac workload and be targeted for the treatment of heart failure. However, the mechanisms regulating cardiomyocyte exocytosis and natriuretic peptide release are still unclear. Our study reveals a novel pathway involving zDHHC9-mediated palmitoylation of Rab3gap1, which impairs exocytosis and limits atrial natriuretic peptide release.
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2023)
Article
Medicine, Research & Experimental
Hadi Khalil, Onur Kanisicak, Ronald J. Vagnozzi, Anne Katrine Johansen, Bryan D. Maliken, Vikram Prasad, Justin G. Boyer, Matthew J. Brody, Tobias Schips, Katja K. Kilian, Robert N. Correll, Kunito Kawasaki, Kazuhiro Nagata, Jeffery D. Molkentin
Article
Cardiac & Cardiovascular Systems
Andrew B. Harvey, Renelyn A. Woltes, Raymond N. Deepe, Hannah G. Tarolli, Jenna R. Drummond, Allison Trouten, Auva Zandi, Jeremy L. Barth, Rupak Mukherjee, Martin J. Romeo, Silvia G. Vaena, Ge Tao, Robin Muise-Helmericks, Paula S. Ramos, Russell A. Norris, Andy Wessels
Summary: This study highlights the importance of SOX9 in the regulation of epicardial cell invasion and emphasizes the role of EPDCs in regulating atrioventricular valve development and homeostasis. It also reports a novel expression profile of Cd109, a gene with previously unknown relevance in heart development.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Review
Cardiac & Cardiovascular Systems
MariaSanta C. Mangione, Jinhua Wen, Dian J. Cao
Summary: mTOR, a mechanistic target of rapamycin, is an evolutionarily conserved pathway that plays a fundamental role in nutrient sensing, growth, metabolism, lifespan, and aging. Recent studies have highlighted the regulatory role of mTOR in innate immune responses and its involvement in the pathogenesis of cardiovascular diseases, especially in acute inflammation and atherosclerotic cardiovascular disease. This review also discusses mTOR's role in trained immunity, immune senescence, and clonal hematopoiesis, as well as its architecture and regulatory complexes.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Junlin Li, Yajun Gong, Yiren Wang, Huihui Huang, Huan Du, Lianying Cheng, Cui Ma, Yongxiang Cai, Hukui Han, Jianhong Tao, Gang Li, Panke Cheng
Summary: Myocardial ischemia-reperfusion injury is closely related to the final infarct size in acute myocardial infarction. Regulatory T cells play an important role in the inflammatory response after AMI, but different subtypes of Tregs have different effects on the injury.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Yuxin Chu, Yutao Hua, Lihao He, Jin He, Yunxi Chen, Jing Yang, Ismail Mahmoud, Fanfang Zeng, Xiaochang Zeng, Gloria A. Benavides, Victor M. Darley-Usmar, Martin E. Young, Scott W. Ballinger, Sumanth D. Prabhu, Cheng Zhang, Min Xie
Summary: This study demonstrates that administering beta-hydroxybutyrate (beta-OHB) at the time of reperfusion can reduce infarct size and preserve cardiac function by activating autophagy and preserving mitochondrial homeostasis, potentially through mTOR inhibition.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)