Article
Biochemistry & Molecular Biology
Rui Wang, Qiqin Xu, Chenlu Wang, Kai Tian, Hui Wang, Xiong Ji
Summary: Proteomic profiling identified ZBTB21 as a transcription factor that contributes to the chromatin binding and transcriptional repression of cohesin in 3D chromatin structures. Other ZBTB factors also interact with cohesin, and double degradation of ZBTB21 and ZBTB7B leads to a further decrease in cohesin chromatin occupancy.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Jose A. da Costa-Nunes, Daan Noordermeer
Summary: Mammalian chromosomes are organized in the cell nucleus at various scales. Topologically Associating Domains (TADs) are structural units that play roles in gene regulation, DNA replication, recombination, and repair. Recent studies suggest that TADs should be interpreted as dynamic collections of actively extruding loops, rather than as insulated domains. This review discusses the emergence of mammalian TAD structure from loop extrusion and the regulatory functions of TAD boundaries.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Letter
Plant Sciences
Mingkun Huang, Ling Zhang, Wai-Shing Yung, Yufang Hu, Zhili Wang, Man-Wah Li, Hon-Ming Lam
Summary: This sentence suggests that the interactions between enhancers, promoters, and transcription factors play a role in mediating the formation of chromatin loops, which in turn regulate downstream gene expression in response to environmental stimuli such as light.
Article
Multidisciplinary Sciences
Dominic D. G. Owens, Giorgio Anselmi, A. Marieke Oudelaar, Damien J. Downes, Alessandro Cavallo, Joe R. Harman, Ron Schwessinger, Akin Bucakci, Lucas Greder, Sara de Ornellas, Danuta Jeziorska, Jelena Telenius, Jim R. Hughes, Marella F. T. R. de Bruijn
Summary: The transcription factor RUNX1 is a critical regulator of developmental hematopoiesis and is frequently disrupted in leukemia. The complex gene Runx1 has two alternative promoters and multiple hematopoietic enhancers. The study reveals that dynamic sub-TAD chromatin boundaries play a role in establishing TAD structure and coordinated gene expression in large multi-promoter developmental genes.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Ken Chen, Huiying Zhao, Yuedong Yang
Summary: This study presents a Transformer-based model, TransEPI, for predicting enhancer-promoter interactions (EPI) by capturing large genomic contexts. TransEPI consistently outperforms other machine learning and deep learning models on datasets from different cell types.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemical Research Methods
Naoto Nishiura, Kunihiko Kaneko
Summary: The research explores how host-parasite interactions affect the evolution of phenotypic variances, indicating that noise in gene expression and genetic diversification play crucial roles in this process.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xue Bai, Feifei Li, Zhihua Zhang
Summary: The study reveals that Alu-derived sequences dominate sequence similarity between enhancers and promoters, and proposes that eRNAs may directly contact targeted promoters by forming trans-acting R-loops at Alu sequences. Functional genomic data, such as RNA-DNA proximate ligation reads, transcription factor binding, and RNA-binding proteins, all align with Alu sequences of EPIs, which may be subject to coevolutionary constraint, indicating the functional significance of these R-loop hybrids.
JOURNAL OF GENETICS AND GENOMICS
(2021)
Article
Biochemical Research Methods
Xiaoping Min, Congmin Ye, Xiangrong Liu, Xiangxiang Zeng
Summary: The paper introduces a method called EPI-DLMH for predicting EPIs using only DNA sequences. By utilizing a convolutional neural network and bidirectional gated recurrent unit network to learn local features and long-range dependencies, as well as incorporating attention mechanism and matching heuristic mechanism, the method shows superior performance in multiple cell lines compared to existing models.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Genetics & Heredity
Mingyang Zhang, Yujia Hu, Min Zhu
Summary: This paper introduces a model called EPIsHilbert, which uses Hilbert curve encoding and transfer learning approaches to predict enhancer-promoter interactions. The model utilizes visualization techniques to explore important sequence fragments, showing high prediction performance and generalization capability across different cell line datasets.
Review
Cell Biology
Christopher M. Uyehara, Effie Apostolou
Summary: The spatiotemporal control of gene expression depends on the activity of regulatory sequences known as enhancers, which regulate target genes over varying distances in the genome. Recent advancements in genomics and imaging technologies have revealed complex networks of enhancer-promoter interactions. This review summarizes our current understanding of enhancer-promoter communication and discusses highly connected enhancer-promoter hubs and their functions in signal integration and gene regulation.
Article
Cell Biology
Kathryn Monfils, Tahsin Stefan Barakat
Summary: Enhancers and promoters are transcriptional regulatory elements that interact to increase gene expression. The mechanism facilitating enhancer-promoter interactions remains unclear, but mutations causing errors in these interactions have been linked to cancer and disease. Multiple models have been proposed to describe how enhancers go the distance to interact with promoters, including loop formation models and more complex hypotheses involving 3D chromatin organization and phase separation.
EUROPEAN JOURNAL OF CELL BIOLOGY
(2021)
Article
Genetics & Heredity
Xingzhong Zhao, Liting Song, Anyi Yang, Zichao Zhang, Jinglong Zhang, Yucheng T. Yang, Xing-Ming Zhao
Summary: This study used CAGE data from the FANTOM5 project to predict enhancer-promoter interactions in 439 human cell and tissue types, and evaluated their reliability. It also examined the genetic heritability and functionality of genes associated with 17 different brain disorders in different neural cell types and tissues. The results showed that the expression of these genes was specific and had distinct expression patterns in different brain regions and developmental stages. This study provides a deeper understanding of the genetic mechanisms underlying brain disorders.
Article
Genetics & Heredity
Mariana Saint Just Ribeiro, Pulak Tripathi, Bahram Namjou, John B. Harley, Iouri Chepelev
Summary: This study elucidates the haplotype-specific mechanisms of gene regulation at 8p23.1 in the human genome and reveals how distal regulatory elements modulate promoter activity, influencing disease risk by changing gene expression. The results provide mechanistic details on how regional variants controlling gene promoters may impact disease risk.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Shuai Liu, Yaqiang Cao, Kairong Cui, Qingsong Tang, Keji Zhao
Summary: This study introduces a proximity ligation-free technique called Hi-TrAC to investigate chromatin interactions among regulatory elements at high-resolution. The research reveals a comprehensive interaction network of regulatory elements across the genome. Cohesin complex and CTCF are found to organize long-range chromatin loops, while ZNF143 and HCFC1 play a role in structuring short-range chromatin loops between regulatory elements, influencing gene expression.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Shinsuke Ito, Nando Dulal Das, Takashi Umehara, Haruhiko Koseki
Summary: The review focuses on emerging views of chromatin conformations associated with enhancer-promoter interactions and the factors that establish or maintain such interactions, which may regulate gene expression. It also discusses various mechanisms that regulate eukaryotic gene expression, including the roles of histone acetylation and methylation, pioneer transcription factors, and architectural proteins.
Article
Multidisciplinary Sciences
Serap Erdogmus, Axel R. Concepcion, Megumi Yamashita, Ikjot Sidhu, Anthony Y. Tao, Wenyi Li, Pedro P. Rocha, Bonnie Huang, Ralph Garippa, Boram Lee, Amy Lee, Johannes W. Hell, Richard S. Lewis, Murali Prakriya, Stefan Feske
Summary: The regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Tiegh Taylor, Natalia Sikorska, Virlana M. Shchuka, Sanjay Chahar, Chenfan Ji, Neil N. Macpherson, Sakthi D. Moorthy, Marit A. C. de Kort, Shanelle Mullany, Nawrah Khader, Zoe E. Gillespie, Lida Langroudi, Ian C. Tobias, Tineke L. Lenstra, Jennifer A. Mitchell, Tom Sexton
Summary: The connection between transcriptional control and chromatin architecture is not clearly understood. This study using genome editing and chromatin interaction analysis in mouse embryonic stem cells found a disconnect where Sox2 transcriptional activation is traced back to a few key transcription factor binding sites that have no effect on promoter-enhancer interaction frequencies or topological domain organization. Maintenance of local chromatin architecture, including at the topologically associating domain boundary downstream from the Sox2 enhancer, is distributed across multiple transcription factor-bound regions and is independent of CTCF. Additionally, disruption of promoter-enhancer interactions has no effect on Sox2 transcription. These findings suggest that many transcription factors can modulate chromatin architecture independently of CTCF.
GENES & DEVELOPMENT
(2022)
Article
Multidisciplinary Sciences
Daisuke Kurotaki, Kenta Kikuchi, Kairong Cui, Wataru Kawase, Keita Saeki, Junpei Fukumoto, Akira Nishiyama, Kisaburo Nagamune, Keji Zhao, Keiko Ozato, Pedro P. Rocha, Tomohiko Tamura
Summary: This study comprehensively determined higher-order chromatin structures by Hi-C in DC progenitors and cDC subpopulations. The results showed that chromatin activation was initially induced at the MDP stage during cDC differentiation, followed by a shift from inactive to active nuclear compartments in CDPs. This study also identified the transcription factor IRF8 as a mediator of chromatin activation and changes in the active compartments in DC progenitors. Furthermore, the study found preestablished chromatin structures of host defense-related gene loci in unstimulated cDCs, which may contribute to the rapid responses to pathogens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Joyce J. Thompson, Daniel J. Lee, Apratim Mitra, Sarah Frail, Ryan K. Dale, Pedro P. Rocha
Summary: The authors demonstrate that the transcription factors NANOG and GATA6 co-bind the same enhancers in common progenitors before the emergence of divergent epiblast and primitive endoderm lineages. This co-binding may play a role in maintaining plasticity and facilitating lineage differentiation. They propose that the co-binding of GATA6 and NANOG at shared enhancers helps maintain the pluripotent state of cells and promotes the establishment of lineage-specific transcriptional programs in epiblast and primitive endoderm.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Christopher T. Rhodes, Joyce J. Thompson, Apratim Mitra, Dhanya Asokumar, Dongjin R. Lee, Daniel J. Lee, Yajun Zhang, Eva Jason, Ryan K. Dale, Pedro P. Rocha, Timothy J. Petros
Summary: The authors utilized a multimodal approach to characterize the transcriptomic and epigenetic landscape of distinct regions in the embryonic mouse forebrain, uncovering diverse chromatin landscapes and regulatory mechanisms. This study is of great significance in enhancing our understanding of neurodevelopment and mechanisms of neurological diseases.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Guojia Xie, Ji-Eun Lee, Anna D. Senft, Young-Kwon Park, Younghoon Jang, Shreeta Chakraborty, Joyce J. J. Thompson, Kaitlin McKernan, Chengyu Liu, Todd S. S. Macfarlan, Pedro P. P. Rocha, Weiqun Peng, Kai Ge
Summary: The enzymatic activities of MLL3 and MLL4 are critical for embryonic development and embryonic stem cell differentiation.
Article
Oncology
Olga Kim, Madison Butler, Zach Sergi, Robert W. Robey, Meili Zhang, Raj Chari, Ying Pang, Guangyang Yu, Wei Zhang, Hua Song, Dionne Davis, Robert G. Hawley, Xinyu Wen, Herui Wang, Martha Quezado, Bao Tran, Mythili Merchant, Alice Ranjan, Frank B. Furnari, Javed Khan, Mark R. Gilbert, Christopher Ryan Miller, Michael M. Gottesman, Yves Pommier, Jing Wu
Summary: The study found that GBM cells lacking PTEN expression are more sensitive to LMP400, but restoring PTEN expression reduces sensitivity to the treatment. Combining LMP400 with Niraparib induces G2/M arrest, DNA damage, suppression of homologous recombination-related proteins, and activates caspase 3/7 activity more significantly in PTEN-null cells compared to PTEN-WT cells. Animal studies confirmed the anti-glioma effect of the drug combination and sufficient BBB penetration.
NEURO-ONCOLOGY ADVANCES
(2023)
Article
Oncology
Olga Lancho, Amartya Singh, Victoria da Silva-Diz, Maya Aleksandrova, Jesminara Khatun, Luca Tottone, Patricia Renck Nunes, Shirley Luo, Caifeng Zhao, Haiyan Zheng, Eric Chiles, Zhenyu Zuo, Pedro P. Rocha, Xiaoyan Su, Hossein Khibaanban, Danie Herran
Summary: We identified a therapeutic vulnerability in T-ALL, where NOTCH1 activates SIRT1 through an enhancer region, and SIRT1 deacetylates and activates KAT7. Targeting SIRT1 shows significant anti-leukemic effects, partly mediated by KAT7 inactivation. This study reveals therapeutic targets in T-ALL and uncovers a regulatory mechanism between deacetylase/acetyltransferase activities.
BLOOD CANCER DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Laura Sala, Manish Kumar, Mahendra Prajapat, Srividya Chandrasekhar, Rachel L. Cosby, Gaspare La Rocca, Todd S. Macfarlan, Parirokh Awasthi, Raj Chari, Michael Kruhlak, Joana A. Vidigal
Summary: AGO2 accumulates in the nucleus of quiescent cells and represses the expression of young retrotransposons by binding to them co-transcriptionally. This study reveals the nuclear function of AGO2 and its role as a genome-defense system in quiescence.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Oncology
Yoshimi Endo Greer, Lidia Hernandez, Emily M. J. Fennell, Manjari Kundu, Donna Voeller, Raj Chari, Samuel F. Gilbert, Thomas S. K. Gilbert, Shashikala Ratnayake, Binwu Tang, Markus Hafner, Qingrong Chen, Daoud Meerzaman, Edwin Iwanowicz, Christina M. Annunziata, Lee M. Graves, Stanley Lipkowitz
Summary: ClpP agonists inhibit breast cancer cell proliferation and CSC function by modulating multiple metabolic pathways essential to CSC function.
CANCER RESEARCH COMMUNICATIONS
(2022)