Article
Multidisciplinary Sciences
Mingyi Yang, Omer Ali, Magnar Bjoras, Junbai Wang
Summary: In this article, a non-coding SNVs analysis tool called bpb3 is proposed to identify functional mutation blocks (FMBs) by integrating genome sequencing and transcriptome data. A two-level Bayesian approach with a biophysical model is implemented to compute TF-DNA binding affinity changes based on clustered position weight matrices (PWMs) from over 1700 TF-motifs. By testing datasets from follicular lymphoma and melanoma, bpb3 automatically and robustly identifies FMBs, providing insights into patho-mechanisms and therapeutic targets.
Article
Biochemical Research Methods
Elias Ulrich, Stefan M. Pfister, Natalie Jaeger
Summary: As non-coding driver mutations become more important in cancer research, a comprehensive and user-friendly software solution for regulatory variant analysis and data visualization is highly relevant. A tool called Revana has been introduced, which can aggregate and visually represent regulatory variants from cancer genomes in a gene-centric manner. It requires whole-genome and RNA sequencing data of a tumor sample cohort and creates interactive HTML reports summarizing the most important regulatory events.
Article
Multidisciplinary Sciences
Prajwal Devkota, Stefan Wuchty
Summary: Understanding tissue-specific transcriptional regulation mechanisms is crucial for preventing diseases. Promoter-binding and enhancer-binding transcription factors play indispensable roles in regulating networks. The genes regulated by these transcription factors have tissue-specific expression and are over-expressed in corresponding cancers. Target genes of enhancer-binding transcription factors are enriched with disease and signaling genes, and these genes are over-expressed in blood-related cancers.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Samah El Ghamrasni, Rene Quevedo, James Hawley, Parisa Mazrooei, Youstina Hanna, Iulia Cirlan, Helen Zhu, Jeff P. Bruce, Leslie E. Oldfield, S. Y. Cindy Yang, Paul Guilhamon, Juri Reimand, Dave W. Cescon, Susan J. Done, Mathieu Lupien, Trevor J. Pugh
Summary: By analyzing primary breast tumors through whole-genome sequencing, we identified transcription factors and cis-regulatory elements associated with the development of breast cancer, providing insights into the driver mechanisms of breast cancer.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Marketa Tomkova, Jakub Tomek, Julie Chow, John D. McPherson, David J. Segal, Fereydoun Hormozdiari
Summary: The study presents a novel framework called Dr.Nod for the detection of non-coding cis-regulatory candidate driver mutations. Applying the framework to tumor data reveals an enrichment of candidate driver mutations in regulatory regions of known cancer driver genes. The study demonstrates the significance of tissue-matched enhancer-gene maps and functional impact of non-coding regulatory driver mutations in cancer.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Yiqun Zhang, Fengju Chen, Erin Pleasance, Laura Williamson, Cameron J. Grisdale, Emma Titmuss, Janessa Laskin, Steven J. M. Jones, Isidro Cortes-Ciriano, Marco A. Marra, Chad J. Creighton
Summary: The study found that somatic structural variants (SVs) have an impact on gene regulation in advanced tumors, leading to altered expression of hundreds of genes near SV breakpoints. Some of these SV-expression associations are correlated with patient survival rates, while a high overall SV burden is associated with treatment using specific drugs.
Review
Biochemistry & Molecular Biology
Arina O. Degtyareva, Elena Antontseva, Tatiana Merkulova
Summary: Many genetic variants affecting gene expression are found in the noncoding part of the genome, mainly through alterations in transcription factor binding. Advanced methods such as eQTL analysis and searching for allele-specific events in various sequencing data are used to identify regulatory variants and understand their functionality.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Melissa Shizue de Almeida Yamashita, Luna Nascimento Vargas, Eduardo de Oliveira Melo
Summary: Researchers isolated and characterized the bovine MUC2 promoter region by designing primers, conducting deletions, and performing transient transfection assays in cell culture experiments, demonstrating its ability to induce expression of a reporter gene.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Hanna Grasshoff, Helge Mueller-Fielitz, Godwin K. Dogbevia, Jakob Koerbelin, Jacqueline Bannach, Carl M. G. Vahldieck, Kristina Kusche-Vihrog, Olaf Joehren, Oliver J. Mueller, Ruben Nogueiras, Vincent Prevot, Markus Schwaninger
Summary: By studying the combination of truncated promoters of brain endothelial-specific genes and short regulatory elements, new regulatory sequences have been developed that efficiently control gene expression in brain endothelial cells with greater strength and specificity.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Agriculture, Dairy & Animal Science
Kaster Nurgulsim, Rajwali Khan, Sayad Haidar Abbas Raza, Amel Ayari-Akkari, Mouna Jeridi, Ijaz Ahmad, Uroosa Mumtaz Arain, Ayman Hassan Abd El-Aziz, Hamayun Khan, Linsen Zan
Summary: This study identifies significant associations between SNPs in the FGF10 gene and body measurement and carcass quality traits in Qinchuan beef cattle, showing high levels of polymorphism.
ANIMAL BIOTECHNOLOGY
(2023)
Article
Agriculture, Dairy & Animal Science
Xianlin Zhao, Rajwali Khan, Guo Hongfang, Sayed Haidar Abbas Raza, Amel Ayari-Akkari, Gehan Othman, Ahmed Mohajja Alshammari, Bandar Hamad Aloufi, Khulood Fahad Alabbosh, Wasimah B. Alshammari, Zan Linsen
Summary: In this study, sequencing of the TORC1 prompter region identified three SNPs at specific loci, which were found to be associated with body measurement and carcass quality traits in Qinchuan beef cattle.
ANIMAL BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yue Gao, Xin Li, Shipeng Shang, Shuang Guo, Peng Wang, Dailin Sun, Jing Gan, Jie Sun, Yakun Zhang, Junwei Wang, Xinyue Wang, Xia Li, Yunpeng Zhang, Shangwei Ning
Summary: LincSNP 3.0 is an updated comprehensive database that focuses on documenting and annotating disease or phenotype-associated variants in human long non-coding RNAs and circular RNAs, with expanded types of variants and regulatory elements, as well as identified associations among them.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Plant Sciences
Prakash Babu Adhikari, Shaowei Zhu, Xiaoyan Liu, Chen Huang, Liyang Xie, Xiaoyan Wu, Jiale He, Nobutaka Mitsuda, Benjamin Peters, Lynette Brownfield, Shingo Nagawa, Ryushiro Dora Kasahara
Summary: The study reveals that MYB98 is specifically expressed in the synergid cells, playing a vital role in pollen tube attraction towards the female gametophyte. The normal expression of MYB98 depends on a cis-regulatory element called SaeM. This element is present in the promoters of SC-specific genes and MYB98 homologous genes in the Brassicaceae.
FRONTIERS IN PLANT SCIENCE
(2023)
Article
Multidisciplinary Sciences
Martin Bostrom, Erik Larsson
Summary: This article introduces a method based on mutation status patterns to independently detect cancer driver genes in tumor genomes, and identifies potential driver genes in melanoma and other cancer types.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Joana Ropio, Martina Prochazkova-Carlotti, Rui Batista, Ana Pestana, Alain Chebly, Jacky Ferrer, Yamina Idrissi, David Cappellen, Cecilia Duraes, Paula Boaventura, Joao Vinagre, Lamia Azzi-Martin, Sandrine Poglio, Jose Cabecadas, Manuel Antonio Campos, Marie Beylot-Barry, Manuel Sobrinho-Simoes, Jean-Philippe Merlio, Paula Soares, Edith Chevret
Summary: Understanding the contribution of telomerase to cancer is important for targeted therapies, especially in primary cutaneous T-cell lymphomas (CTCL) where there is limited data. This study found that certain SNPs in the hTERT gene and post-transcriptional regulation of hTERT could influence the occurrence of CTCL. The results highlight the role of telomerase in CTCL and suggest a potential new role for hTERT variants.
Article
Genetics & Heredity
Gabriella E. Martyn, Beeke Wienert, Lu Yang, Manan Shah, Laura J. Norton, Jon Burdach, Ryo Kurita, Yukio Nakamura, Richard C. M. Pearson, Alister P. W. Funnell, Kate G. R. Quinlan, Merlin Crossley
Article
Biochemistry & Molecular Biology
Alexander J. Knights, Emily J. Vohralik, Kyle L. Hoehn, Merlin Crossley, Kate G. R. Quinlan
Article
Hematology
Gabriella E. Martyn, Beeke Wienert, Ryo Kurita, Yukio Nakamura, Kate G. R. Quinlan, Merlin Crossley
Review
Genetics & Heredity
Beeke Wienert, Gabriella E. Martyn, Alister P. W. Funnell, Kate G. R. Quinlan, Merlin Crossley
TRENDS IN GENETICS
(2018)
Article
Biochemistry & Molecular Biology
Manan Shah, Alister P. W. Funnell, Kate G. R. Quinlan, Merlin Crossley
Article
Biochemistry & Molecular Biology
Alexander J. Knights, Lu Yang, Manan Shah, Laura J. Norton, Gamran S. Green, Elizabeth S. Stout, Emily J. Vohralik, Merlin Crossley, Kate G. R. Quinlan
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Lu Yang, Zhiliang Chen, Elizabeth S. Stout, Fabien Delerue, Lars M. Ittner, Marc R. Wilkins, Kate G. R. Quinlan, Merlin Crossley
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Alexander J. Knights, Emily J. Vohralik, Peter J. Houweling, Elizabeth S. Stout, Laura J. Norton, Stephanie J. Alexopoulos, Jinfen. J. Yik, Hanapi Mat Jusoh, Ellen M. Olzomer, Kim S. Bell-Anderson, Kathryn N. North, Kyle L. Hoehn, Merlin Crossley, Kate G. R. Quinlan
NATURE COMMUNICATIONS
(2020)
Editorial Material
Multidisciplinary Sciences
John S. Dryzek, Dianne Nicol, Simon Niemeyer, Sonya Pemberton, Nicole Curato, Andre Bachtiger, Philip Batterham, Bjorn Bedsted, Simon Burall, Michael Burgess, Gaetan Burgio, Yurij Castelfranchi, Herve Chneiweiss, George Church, Merlin Crossley, Jantina de Vries, Mahmud Farooque, Marit Hammond, Baogang He, Ricardo Mendonca, Jennifer Merchant, Anna Middleton, John E. J. Rasko, Ine Van Hoyweghen, Antoine Vergne
Article
Biochemistry & Molecular Biology
Xianjiang Lan, Ren Ren, Ruopeng Feng, Lana C. Ly, Yemin Lan, Zhe Zhang, Nicholas Aboreden, Kunhua Qin, John R. Horton, Jeremy D. Grevet, Thiyagaraj Mayuranathan, Osheiza Abdulmalik, Cheryl A. Keller, Belinda Giardine, Ross C. Hardison, Merlin Crossley, Mitchell J. Weiss, Xiaodong Cheng, Junwei Shi, Gerd A. Blobel
Summary: ZNF410 is a pentadactyl DNA-binding protein that activates only one gene, CHD4, in human erythroid cells. Loss of ZNF410 leads to decreased CHD4 levels and derepression of fetal hemoglobin genes, revealing their sensitivity to reduced CHD4 levels. The specific binding sites near the CHD4 gene provide the specificity of ZNF410's transcriptional activation in erythroid cells.
Article
Genetics & Heredity
Phillip A. Doerfler, Ruopeng Peng, Yichao Li, Lance E. Palmer, Shaina N. Porter, Henry W. Bell, Merlin Crossley, Shondra M. Pruett-Miller, Yong Cheng, Mitchell J. Weiss
Summary: Hereditary persistence of fetal hemoglobin variants activate gamma-globin expression through distinct mechanisms involving transcription factors, providing insights for therapeutic genome editing and gene therapies targeting this element.
Article
Genetics & Heredity
Peng Huang, Scott A. Peslak, Ren Ren, Eugene Khandros, Kunhua Qin, Cheryl A. Keller, Belinda Giardine, Henry W. Bell, Xianjiang Lan, Malini Sharma, John R. Horton, Osheiza Abdulmalik, Stella T. Chou, Junwei Shi, Merlin Crossley, Ross C. Hardison, Xiaodong Cheng, Gerd A. Blobel
Summary: HIC2 regulates the fetal-to-adult hemoglobin switch by inhibiting the transcription of the BCL11A gene through reducing chromatin accessibility and displacing the GATA1 transcription factor. It plays a crucial role in the developmental control of BCL11A and is important for hemoglobin switching.
Review
Genetics & Heredity
Merlin Crossley, Georgios E. Christakopoulos, Mitchell J. Weiss
Summary: Sickle cell disease is a common genetic blood disorder that causes acute and chronic pain, multiorgan damage, and early death. Recent advancements in technology and research have made curing most patients possible, and there is ongoing exploration of more accessible treatments.
TRENDS IN GENETICS
(2022)
Article
Hematology
Sarah K. Topfer, Ruopeng Feng, Peng Huang, Lana C. Ly, Gabriella E. Martyn, Gerd A. Blobel, Mitchell J. Weiss, Kate G. R. Quinlan, Merlin Crossley
Summary: This study systematically analyzes the deletions associated with HPFH and 6B-thalassemia, and proposes a unifying mechanism: the deletion of the proximal adult B-globin (HBB) promoter in all cases where fetal globin is upregulated. Experimental results show that mutations reducing HBB promoter activity lead to elevated fetal globin expression.
Article
Cell Biology
Yang Yang, Ren Ren, Lana C. Ly, John R. Horton, Fudong Li, Kate G. R. Quinlan, Merlin Crossley, Yunyu Shi, Xiaodong Cheng
Summary: The study uncovered ZBTB7A/LRF as a key molecular regulator of fetal globin expression, with mutations affecting its DNA binding ability, informing genome-editing strategies for treating hemoglobinopathies.