Article
Biochemistry & Molecular Biology
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Roderick A. F. MacLeod
Summary: Aberrantly activated NKL homeobox genes NKX2-3 and NKX2-4 have been identified in AML, disrupting genes involved in megakaryocytic and erythroid differentiation processes, thus contributing to the formation of specific AML subtypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Jennifer Steens, Diana Klein
Summary: Stem cells have the unique ability to self-renew and differentiate into specialized cells. Adult stem cells exhibit limited differentiation capabilities determined by their tissue of origin. HOX genes, as master regulators of cell identity and fate, play a role in embryogenesis and maintaining positional identity. Understanding the regulation of HOX genes in stem cells may lead to advancements in regenerative medicine.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Nikhil Hajirnis, Rakesh K. Mishra
Summary: Hox genes, responsible for regulating the anterior-posterior body axis in animals, exhibit diversity in arrangement across different organisms. Minor changes in gene expression levels play a significant role in the development of biological features, impacting primary axis formation, segment identity, and other crucial processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Developmental Biology
Katharine A. Hubert, Deneen M. Wellik
Summary: Hox genes play a crucial role in the proper development of bilaterian organisms and their expression is tightly regulated by their unique genomic organization. While their genetic function during embryonic development is well-studied, less is known about how these transcription factors regulate downstream genes to direct morphogenetic events. Additionally, the continued expression and function of Hox genes at postnatal and adult stages emphasize their importance throughout an organism's lifespan.
Article
Cell Biology
Wei Tian, Kegong Chen, Guangcan Yan, Xinhao Han, Yanlong Liu, Qiuju Zhang, Meina Liu
Summary: This study identified eRNA-regulated immune-related genes (IRGs) in gliomas and constructed a novel prognostic model. The regulation of these IRGs by eRNAs was associated with immune-related dysfunctions in the tumor microenvironment. Targeting these IRGs could improve immunotherapeutic/therapeutic outcomes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Narendra P. Singh
Summary: This study demonstrates how the Hox transcription factor Ultrabithorax acts as both a repressor and an activator in a cell type-specific manner to alter chromatin accessibility and gene regulation.
Article
Biochemistry & Molecular Biology
Stefan Nagel, Corinna Meyer
Summary: This study investigated TALE homeobox genes in early B-cell development and identified aberrant activities of IRX2, IRX3, and MEIS1 in specific subtypes of BCP-ALL. These genes may serve as novel diagnostic markers and therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Roderick A. F. MacLeod
Summary: Homeobox genes encode transcription factors that control basic developmental decisions, and their hematopoietic activities have implications for both normal and malignant immune cell development. By constructing lymphoid TALE-code and myeloid TALE-code, expression patterns of active TALE class homeobox genes in early hematopoiesis and lymphopoiesis were revealed, providing insights into the regulatory roles of these genes in AML and identifying potential oncogenic activities when deregulated. Further analysis of gene expression and knockout experiments in AML cell lines demonstrated the impact of IRX factors in normal and malignant myeloid differentiation, suggesting potential therapeutic targets for AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Aishwarya Gurumurthy, David T. Yu, Jared R. Stees, Pamela Chamales, Ekaterina Gavrilova, Paul Wassel, Lu Li, Daniel Stribling, Jinyang Chen, Marissa Brackett, Alexander M. Ishov, Mingyi Xie, Jorg Bungert
Summary: SEs mediate high transcription levels by recruiting transcription complexes and generating eRNAs. The LCR is able to recruit transcription complexes independently from linked genes, and HS2 initiates bidirectional transcription. Integrator complex plays a role in terminating eRNA transcription and interacts downstream of LCR HS2, affecting transcription of beta-globin genes.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Developmental Biology
Olivia R. A. Tidswell, Matthew A. Benton, Michael Akam
Summary: The neuroblast timer genes hunchback, Kruppel, nubbin, and castor are expressed sequentially in the segment addition zone of the beetle Tribolium, with nubbin shown to regulate segment identity redundantly with other gap/gap-like genes. Knockdown of nubbin, along with giant and knirps, results in homeotic transformation with ectopic legs, likely due to expanded Kruppel expression and loss of abdominal Hox gene expression. These findings support the theory that the neuroblast timer series was co-opted for insect segment patterning and contribute to understanding the evolution and function of the gap gene network beyond Drosophila.
Article
Multidisciplinary Sciences
Jin-Xiu Li, Xue-Zhen Huang, Wei-ping Fu, Xiao-hua Zhang, David H. Mauki, Jing Zhang, Chang Sun, Lu-Ming Dai, Li Zhong, Li Yu, Ya-ping Zhang
Summary: This study conducted comprehensive bioinformatics analyses and experimental verifications to explore the regulatory mechanism of rs10516526 and GSTCD in COPD. The results showed that low expression of GSTCD was associated with COPD, and the transcription factors C-Jun and CREB1 were found to be essential for the regulation of GSTCD by specific genetic signals. Moreover, certain mutated forms of these signals showed a stronger binding ability to the transcription factors, potentially leading to allele-specific regulation and reduced susceptibility to COPD.
Article
Biochemical Research Methods
Danni Hong, Hongli Lin, Lifang Liu, Muya Shu, Jianwu Dai, Falong Lu, Mengsha Tong, Jialiang Huang
Summary: This study introduces an algorithm, eNet, to build enhancer networks in single cells, providing insights into the regulatory relationships among enhancers and their role in controlling cell identity and disease genes. The study finds that complex enhancer networks are important in regulating gene expression and predicting cell identity and disease genes.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Cell Biology
Alexandra D. Buffry, Sebastian Kittelmann, Alistair P. McGregor
Summary: Hox genes determine the regional identity of animal bodies during embryogenesis and play a role in post-embryonic fine-scale morphology. In Drosophila melanogaster, the Ultrabithorax (Ubx) gene regulates bristle and trichome patterning on the femurs of the second and third leg pairs. The repression of trichomes in the proximal posterior region of the T2 femur by Ubx is mediated by the activation of microRNA-92a and microRNA-92b. Additionally, a novel enhancer of Ubx that recapitulates its temporal and regional activity in T2 and T3 legs has been identified, along with transcription factors and co-factors that regulate trichome patterning.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Correction
Multidisciplinary Sciences
A. Marshall, J. Kasturiarachchi, P. Datta, Y. Guo, E. Deltcheva, C. James, J. Brown, G. May, N. Anandagoda, I. Jackson, J. K. Howard, E. Ghazaly, S. Brooks, A. Khwaja, M. Araki, K. Araki, D. Linch, G. M. Lord, T. Enver, R. Nimmo
Summary: The paper has been amended and the updated version can be accessed through a link at the top of the paper.
SCIENTIFIC REPORTS
(2021)
Article
Biochemical Research Methods
Danni Hong, Hongli Lin, Lifang Liu, Muya Shu, Jianwu Dai, Falong Lu, Mengsha Tong, Jialiang Huang
Summary: We propose an algorithm, eNet, to construct enhancer networks by integrating single-cell chromatin accessibility and gene expression profiles. Applying eNet to a human blood dataset, we find that cell identity and disease genes are regulated by complex enhancer networks, with the network hub enhancers being the most important. Compared to super-enhancers, enhancer networks outperform in predicting cell identity and disease genes. Our work presents a model of enhancer networks containing three modes: Simple, Multiple, and Complex, based on the complexity of gene expression regulation. In summary, our study provides an unsupervised approach to identify key cell identity and disease genes and explore the regulatory relationships among enhancers in single cells.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemical Research Methods
Le A. Trinh, Vanessa Chong-Morrison, Tatjana Sauka-Spengler
Article
Multidisciplinary Sciences
Hugo J. Parker, Bony De Kumar, Stephen A. Green, Karin D. Prummel, Christopher Hess, Charles K. Kaufman, Christian Mosimann, Leanne M. Wiedemanm, Marianne E. Bronner, Robb Krumlauf
NATURE COMMUNICATIONS
(2019)
Article
Developmental Biology
Hugo J. Parker, Marianne E. Bronner, Robb Krumlauf
DEVELOPMENTAL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Kerstin Pinkwart, Falk Schneider, Martyna Lukoseviciute, Tatjana Sauka-Spengler, Edward Lyman, Christian Eggeling, Erdinc Sezgin
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Karin D. Prummel, Christopher Hess, Susan Nieuwenhuize, Hugo J. Parker, Katherine W. Rogers, Iryna Kozmikova, Claudia Racioppi, Eline C. Brombacher, Anna Czarkwiani, Dunja Knapp, Sibylle Burger, Elena Chiavacci, Gopi Shah, Alexa Burger, Jan Huisken, Maximina H. Yun, Lionel Christiaen, Zbynek Kozmik, Patrick Mueller, Marianne Bronner, Robb Krumlauf, Christian Mosimann
NATURE COMMUNICATIONS
(2019)
Article
Cell Biology
Irving T. C. Ling, Tatjana Sauka-Spengler
NATURE CELL BIOLOGY
(2019)
Article
Biology
Mohammad KaramiNejadRanjbar, Sahand Sharifzadeh, Nina C. Wietek, Mara Artibani, Salma El-Sahhar, Tatjana Sauka-Spengler, Christopher Yau, Volker Tresp, Ahmed A. Ahmed
Article
Neurosciences
Surangi N. Perera, Ruth M. Williams, Rachel Lyne, Oliver Stubbs, Dennis P. Buehler, Tatjana Sauka-Spengler, Masaharu Noda, Gos Micklem, E. Michelle Southard-Smith, Clare V. H. Baker
Article
Multidisciplinary Sciences
Gi Fay Mok, Leighton Folkes, Shannon A. Weldon, Eirini Maniou, Victor Martinez-Heredia, Alice M. Godden, Ruth M. Williams, Tatjana Sauka-Spengler, Grant N. Wheeler, Simon Moxon, Andrea E. Muensterberg
Summary: This study used ATAC-seq and RNA-seq to analyze the spatiotemporal dynamics along the chick embryonic axis, identifying differential binding site coverage for key transcription factors and connecting accessible chromatin with nearby expressed genes. The authors determined cis-regulatory elements for TCF15 and MEOX1, investigated their spatiotemporal activity and evolutionary conservation, and disrupted their expression through epigenome silencing to recapitulate phenotypic abnormalities of anterior-posterior axis extension. This integrated approach allows for dissection of paraxial mesoderm regulatory circuits in vivo and has implications for investigating gene regulatory networks.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Fei Xu, Ferdinand Marletaz, Daria Gavriouchkina, Xiao Liu, Tatjana Sauka-Spengler, Guofan Zhang, Peter W. H. Holland
Summary: The article discusses the similar expression patterns of Hox and ParaHox genes encoding transcription factors in divergent animals, highlighting the regulatory role of the Pdx gene on the insulin gene in Pacific oysters. The study shows that cgILP gene is co-expressed with cgPdx in oyster digestive tissue, indicating this gene interaction dates back to the origin of Bilateria.
NATURE COMMUNICATIONS
(2021)
Article
Developmental Biology
Hugo J. Parker, Bony De Kumar, Irina Pushel, Marianne E. Bronner, Robb Krumlauf
Summary: Meis genes in lampreys show dynamic expression patterns in the hindbrain and pharynx during development. Enhancers bound by Hox and TALE proteins have been identified in Meis loci of lampreys, mice, and zebrafish. Conserved elements with binding motifs for Hox and TALE proteins suggest ancient regulatory interactions in vertebrate evolution.
DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Vasileios Papadogiannis, Alessandro Pennati, Hugo J. Parker, Ute Rothbacher, Cedric Patthey, Marianne E. Bronner, Sebastian M. Shimeld
Summary: This study investigates the role of the Hmx gene in the development of sensory ganglia in vertebrates. The results demonstrate the conservation of regulatory and functional properties of Hmx between Ciona and vertebrates, and suggest that bipolar tail neurons might be homologous to cranial sensory ganglia.
Article
Multidisciplinary Sciences
Wei Wei, Katherine R. Schon, Greg Elgar, Andrea Orioli, Melanie Tanguy, Adam Giess, Marc Tischkowitz, Mark J. Caulfield, Patrick F. Chinnery
Summary: The transfer of mitochondrial DNA into the nucleus contributes to a complex landscape of nuclear-mitochondrial segments (NUMTs). Almost all individuals have multiple NUMTs, including rare ones that are present in less than 0.1% of the population. Most NUMTs inserted into the nuclear genome after humans diverged from apes. Once inserted, the sequences are no longer under mitochondrial evolutionary constraints and have different mutational signatures compared to mitochondrial DNA.
Review
Genetics & Heredity
Oana Pelea, Tudor A. A. Fulga, Tatjana Sauka-Spengler
Summary: CRISPR-Cas9 has become a major tool for genome manipulation. Recent studies have shown that the activity of CRISPR can be controlled by sensing the expression levels of endogenous transcripts, which is of great significance for studying cell types, disease states, and environmental challenges.
Article
Biology
Vanessa Chong-Morrison, Sarah Mayes, Filipa C. Simoes, Upeka Senanayake, Dervla S. Carroll, Paul R. Riley, Stephen W. Wilson, Tatjana Sauka-Spengler
Summary: Due to its genetic amenability coupled with advances in genome editing, zebrafish is an excellent model to examine the function of (epi)genomic elements. We repurposed the Ac/Ds maize transposition system to efficiently characterise zebrafish cis-regulated elements, also known as enhancers, in F0-microinjected embryos. We used the system to stably express guide RNAs enabling CRISPR/dCas9-interference (CRISPRi) perturbation of enhancers without disrupting the underlying genetic sequence. In addition, we probed the phenomenon of antisense transcription at two neural crest gene loci. Our study highlights the utility of Ac/Ds transposition as a new tool for transient epigenome modulation in zebrafish.