Review
Multidisciplinary Sciences
Jason H. Brickner
Summary: This article discusses the mechanisms by which histone modifications can be inherited and relates them to the phenomenon of epigenetic transcriptional memory. Recent studies have found that the histone H3 lysine 4 dimethylation associated with this memory plays a critical role in sustaining memory and can be stably maintained through multiple mitoses. This chromatin-mediated inheritance mechanism involves a physical interaction between an H3K4me2 reader, SET3C, and an H3K4me2 writer, Spp1(-) COMPASS. This is the first example of chromatin-mediated inheritance of a mark that promotes transcription.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Multidisciplinary Sciences
Lucia Ramos-Alonso, Petter Holland, Stephanie Le Gras, Xu Zhao, Bernard Jost, Magnar Bjoras, Yves Barral, Jorrit M. Enserink, Pierre Chymkowitch
Summary: Mitotic entry is associated with a series of cellular changes in chromosomes and transcription factors, leading to downregulation of transcription. However, the influence of mitotic condensation on transcription during interphase is unknown. In this study, we found that failure to condense a specific chromosome during mitosis resulted in aberrant transcription in the subsequent interphase, leading to high expression levels of genes in cis and the activation of inducible transcriptional programs in trans. These findings reveal an unexpected role of mitosis and mitotic chromosome condensation in maintaining transcriptional homeostasis during interphase.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
J. Peter Svensson
Summary: HIV-1 integrates as a provirus in the host genome, forming a reservoir of infected cells similar to oncogenes. Both HIV-1 provirus and oncogenes require expression to cause disease. Successful cure for HIV-1 and cancer involves eliminating cells with potential to regenerate the disease, and epigenetic drugs used against cancer have been applied in HIV-1 field to modulate the proviral chromatin state.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biology
Bethany Sump, Donna G. Brickner, Agustina D'Urso, Seo Hyun Kim, Jason H. Brickner
Summary: The rate and mechanism of transcriptional activation for certain genes depend on the cell's prior experiences, known as epigenetic transcriptional memory. In yeast, memory of inositol starvation involves interactions between transcription factors and the nuclear pore complex, as well as changes in chromatin structure. This memory process accelerates reactivation.
Review
Oncology
Siwei Deng, Yuliang Feng, Siim Pauklin
Summary: This review discusses the importance of three-dimensional chromatin structures in biological processes and diseases, as well as the key structural protein elements involved in chromatin interactions. The recent development of technologies and bioinformatics approaches for studying chromatin interactions in gene expression regulation is also summarized.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Zhengtao Xiao, Jason W. Locasale
Summary: Chromatin and associated epigenetic marks provide important platforms for gene regulation in response to metabolic changes associated with environmental exposures. Studies have shown that fluctuations of key metabolites can influence chromatin modifications, but their effects on chromatin structure are largely unknown.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2021)
Review
Dermatology
Ramile Dilshat, Hong Nhung Vu, Eirikur Steingrimsson
Summary: Melanocytes originate in the neural crest, migrate and proliferate before differentiating into pigment-producing cells, determining color and protecting against UV radiation; their lineage is regulated by transcription factors and signaling pathways, with epigenetic modifiers and replacement histones playing key roles in this process.
EXPERIMENTAL DERMATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Maria Theresia Watzlowik, Sujaan Das, Markus Meissner, Gernot Laengst
Summary: The gene transcription regulation of the human malaria parasite Plasmodium falciparum is governed by complex epigenetic mechanisms involving chromatin structure and dynamics. The high AT-content of the parasite genome and sequence divergence of chromatin-related proteins suggest significant differences in chromatin-dependent regulation compared to other eukaryotes. Specialized chromatin remodeling enzymes play an essential role in gene regulation in P. falciparum.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Joshua A. R. Brown, Jieying Hazel Cui, Maggie Y. M. Ling, Ellia X. C. Gao, LeAnn J. Howe, Sheila S. Teves, James Davie
Summary: The 43rd Asilomar Chromatin, Chromosomes, and Epigenetics Conference was held online, allowing researchers at different career stages to share promising new findings. The conference covered modern chromatin research in various model systems and explored the fundamental principles of nuclear organization and transcription regulation, as well as key mechanisms underlying human disease.
BIOCHEMISTRY AND CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Joshua A. R. Brown, Jieying Hazel Cui, Maggie Y. M. Ling, Ellia X. C. Gao, LeAnn J. Howe, Sheila S. Teves
Summary: The 43rd Asilomar Chromatin, Chromosomes, and Epigenetics Conference provided a platform for researchers at various career stages to share promising new findings in the field of chromatin research. The conference covered a wide range of topics, including nuclear organization, transcription regulation, and mechanisms underlying human diseases.
BIOCHEMISTRY AND CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Osama Garwain, Xiaoming Sun, Divya Ramalingam Iyer, Rui Li, Lihua Julie Zhu, Paul D. Kaufman
Summary: The depletion of Ki-67 in vertebrate mammals can cause DNA damage, particularly in mitotic cells. The C-terminal chromatin-binding domain of Ki-67 plays a crucial role in protecting cells from this damage. Simultaneous depletion of Ki-67 and p53 results in increased chromosome bridges and micronuclei, highlighting the importance of Ki-67 in maintaining genome stability.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Peerapat Khamwachirapithak, David Guillaume-Schoepfer, Pakkanan Chansongkrow, Sarah A. Teichmann, Philip A. Wigge, Varodom Charoensawan
Summary: This study combines ChIP-seq and RNA-seq to investigate the effects of global and local H3 depletion on gene transcription, as well as the interaction between the transcription factor Rap1 and H3. The results provide a working model and testable hypotheses regarding the impact of H3 depletion on transcriptional changes.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Review
Microbiology
Stephen M. Matthews, Ian J. Groves, Christine M. O'Connor
Summary: Human cytomegalovirus (HCMV) is a betaherpesvirus that establishes lifelong infection in its host and can cause severe comorbidities in individuals with suppressed or compromised immune systems. The lifecycle of HCMV consists of lytic and latent phases, largely dependent upon the cell type infected and whether transcription from the major immediate early locus can ensue. Epigenetic regulation through chromatinization, chromatin modifiers, and transcription factor recruitment play important roles in controlling gene expression from the HCMV genome during infection.
Review
Cell Biology
Amritha Sreekumar, Sharanjot Saini
Summary: Therapy-induced neuroendocrine prostate cancer (NEPC) is a highly aggressive variant of prostate cancer that arises through a reversible process called neuroendocrine differentiation (NED). NED involves decreased expression of androgen receptor (AR) and increased expression of neuroendocrine lineage markers. This article reviews the role of transcription factors and chromatin modifiers in driving lineage reprogramming and discusses the potential for better therapeutic strategies to target NEPC.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Dakota L. Jones, Grey F. Hallstroem, Xi Jiang, Ryan C. Locke, Mary Kate Evans, Edward D. Bonnevie, Anjana Srikumar, Thomas P. Leahy, Madhura P. Nijsure, Joel D. Boerckel, Robert L. Mauck, Nathaniel A. Dyment
Summary: Cells integrate mechanical cues to maintain tissue function and homeostasis, but the underlying mechanisms are not well understood. This study shows that loss of tensile cues changes nuclear morphology, positioning, and gene expression, resulting in weakening of tendons.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Justin Jee, Aaron J. Stonestrom, Sean Devlin, Teresa Nguyentran, Beatriz Wills, Varun Narendra, Michael B. Foote, Melissa Lumish, Santosha A. Vardhana, Stephen M. Pastores, Neha Korde, Dhwani Patel, Steven Horwitz, Michael Scordo, Anthony F. Daniyan
Summary: This retrospective study investigated the impact of different medications commonly used in cancer treatment on the outcomes of cancer patients infected with SARS-CoV-2. The results suggested that corticosteroid administration may lead to worse outcomes in some cases, while the effects of chemotherapy or immunotherapy on the prognosis of COVID-19 in cancer patients remain unclear.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Li Cheng, Yichao Li, Qian Qi, Peng Xu, Ruopeng Feng, Lance Palmer, Jingjing Chen, Ruiqiong Wu, Tiffany Yee, Jingjing Zhang, Yu Yao, Akshay Sharma, Ross C. Hardison, Mitchell J. Weiss, Yong Cheng
Summary: This study identifies regulatory noncoding nucleotides in four loci controlling erythroid fetal hemoglobin (HbF) expression, revealing the genetic complexities of HbF regulation and providing potential therapeutic insights into sickle cell disease (SCD). Targeting a repressor element raises HbF levels in cells from SCD patients.
Article
Genetics & Heredity
Cheryl A. Keller, Alexander Q. Wixom, Elisabeth F. Heuston, Belinda Giardine, Chris C-S Hsiung, Maria R. Long, Amber Miller, Stacie M. Anderson, April Cockburn, Gerd A. Blobel, David M. Bodine, Ross C. Hardison
Summary: The study focused on the importance of sonication in ChIP-seq experiments, finding that the level of sonication significantly impacts the quality of ChIP-seq signals. Over-sonication consistently reduces quality, while under-sonication affects binding by different transcription factors differently.
G3-GENES GENOMES GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Bowen Yan, Jennifer Yang, Min Young Kim, Huacheng Luo, Nicholas Cesari, Tao Yang, John Strouboulis, Jiwang Zhang, Ross Hardison, Suming Huang, Yi Qiu
Summary: The activity of hematopoietic factor GATA-1 is modulated by acetylation and deacetylation processes mediated by HDAC1, allowing for chromatin binding and transcriptional regulation of erythroid/megakaryocyte commitment and differentiation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Haoyue Zhang, Jessica Lam, Di Zhang, Yemin Lan, Marit W. Vermunt, Cheryl A. Keller, Belinda Giardine, Ross C. Hardison, Gerd A. Blobel
Summary: During mitosis, transcription is globally attenuated and chromatin architecture is dramatically reconfigured. Loss of the architectural factor CTCF results in failure to form structural loops, leading to inappropriate cis-regulatory contacts and alterations of compartmental interactions after mitosis. While global 3D architecture is set up without transcription, ongoing transcription contributes significantly to the formation of gene domains.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Kelly Cochran, Divyanshi Srivastava, Avanti Shrikumar, Akshay Balsubramani, Ross C. Hardison, Anshul Kundaje, Shaun Mahony
Summary: The DNA sequence preferences and cooperative partners of transcription factors (TFs) are conserved across species. However, predicting TF binding in one species based on sequence models of a closely related species is challenging due to species-specific repeats. To address this challenge, researchers used neural networks to predict TF binding across species and found that the predictive performance was worse than within-species predictions. By using an augmented network architecture, they were able to correct for prediction errors caused by species-specific repeats and improve the overall cross-species model performance.
Article
Biochemistry & Molecular Biology
Kiara N. Berrios, Niklaus H. Evitt, Rachel A. DeWeerd, Diqiu Ren, Meiqi Luo, Aleksia Barka, Tong Wang, Caroline R. Bartman, Yemin Lan, Abby M. Green, Junwei Shi, Rahul M. Kohli
Summary: The study focuses on DNA deaminase enzymes and their application in biotechnology. Split-engineered BEs (seBEs) have been developed to provide small-molecule control over targeted mutator activity, offering a solution for temporally controlling precision genome editing.
NATURE CHEMICAL BIOLOGY
(2021)
Editorial Material
Hematology
Ross C. Hardison
Summary: In this study, Topfer et al use a combination of natural history and modern genome editing techniques to provide evidence for the role of promoter competition in the switching of hemoglobin production. Their findings offer promising therapeutic approaches for inherited hemoglobin disorders and resolve a long-standing issue, proposing a unifying model.
Article
Biochemistry & Molecular Biology
Karun Kiani, Eric M. Sanford, Yogesh Goyal, Arjun Raj
Summary: A major goal in the field of transcriptional regulation is to understand the relationship between transcription factor binding and gene expression changes. This study used ATAC-seq and RNA-seq measurements to examine the concordance between chromatin accessibility changes and expression changes in response to specific perturbations. The results showed that some genes exhibited changes in both accessibility and expression, while others showed changes in expression without corresponding changes in accessibility. The findings suggest that gene expression changes can occur independently of changes in chromatin accessibility.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Caroline R. R. Bartman, Daniel R. R. Weilandt, Yihui Shen, Won Dong Lee, Yujiao Han, Tara TeSlaa, Connor S. R. Jankowski, Laith Samarah, Noel R. R. Park, Victoria da Silva-Diz, Maya Aleksandrova, Yetis Gultekin, Argit Marishta, Lin Wang, Lifeng Yang, Asael Roichman, Vrushank Bhatt, Taijin Lan, Zhixian Hu, Xi Xing, Wenyun Lu, Shawn Davidson, Martin Wuehr, Matthew G. G. Vander Heiden, Daniel Herranz, Jessie Yanxiang Guo, Yibin Kang, Joshua D. D. Rabinowitz
Summary: In this study, the rates of glycolysis and the tricarboxylic acid (TCA) cycle were measured in various mouse tissues and cancer models. The research found that TCA cycle flux was suppressed in solid tumors and increased in lung metastases of breast cancer. Although glycolysis was increased in tumors, it was not enough to compensate for the low TCA flux in terms of ATP production. This suggests that solid tumors generally produce ATP at a slower rate than normal.
Article
Multidisciplinary Sciences
Hillary Koch, Cheryl A. Keller, Guanjue Xiang, Belinda Giardine, Feipeng Zhang, Yicheng Wang, Ross C. Hardison, Qunhua Li
Summary: Comparing experimental results across multiple different conditions can be more precise and meaningful. Researchers have introduced a method called CLIMB that allows for this type of comparison and captures interpretable and biologically meaningful information.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Kunhua Qin, Xianjiang Lan, Peng Huang, Megan S. Saari, Eugene Khandros, Cheryl A. Keller, Belinda Giardine, Osheiza Abdulmalik, Junwei Shi, Ross C. Hardison, Gerd A. Blobel
Summary: BMI1, a subunit of PRC1, is identified as a novel repressor of fetal hemoglobin (HbF) and regulates this process through its target genes LIN28B, IGF2BP1, and IGF2BP3. PRC1 and PRC2 work together to repress HbF expression, revealing an epigenetic mechanism involved in hemoglobin switching.
Review
Medicine, Research & Experimental
Michael R. Waarts, Aaron J. Stonestrom, Young C. Park, Ross L. Levine
Summary: Targeted therapies have become increasingly important in cancer treatment, with technological advances improving our understanding of genetic mutations in tumors. In some cases, targeted therapy has dramatically improved treatment outcomes and disease prognoses.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Endocrinology & Metabolism
Caroline R. Bartman, Tara TeSlaa, Joshua D. Rabinowitz
Summary: The article provides a detailed review of techniques for measuring metabolic fluxes in intact mammals and emphasizes the importance of measuring metabolism in vivo. Researchers studying glucose homeostasis have developed strategies that have been strengthened by recent advances in metabolomics technologies, with promising avenues for future application. The broader application of these methods has the potential to accelerate biomedical progress given the significant importance of metabolism to health and disease.
Article
Biochemistry & Molecular Biology
Belinda Giardine, Philippe Joly, Serge Pissard, Henri Wajcman, David H. K. Chui, Ross C. Hardison, George P. Patrinos
Summary: HbVar is a widely used locus-specific database that provides information on genomic variants related to hemoglobin variants and thalassemia. The database has been updated with clinically relevant information, improved querying options, user-friendly interface, and expanded data content for increased utility in clinical settings.
NUCLEIC ACIDS RESEARCH
(2021)