Review
Cell Biology
Laura Prendergast, Danny Reinberg
Summary: Recent advances in chromatin and epigenetics research have highlighted the significance of core histones, histone variants, and their post-translational modifications in regulating chromatin structure. The role of linker histone H1, which was previously understudied, has come into focus due to its evolutionary conservation, variability in PTMs, and unique functions across different cell types. Contrary to previous assumptions, histone H1 variants are now recognized for their independent roles in various chromatin-based processes, challenging the traditional view of their function solely in chromatin compaction and transcriptional repression.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Nuria Serna-Pujol, Monica Salinas-Pena, Francesca Mugianesi, Francois Le Dily, Marc A. Marti-Renom, Albert Jordan
Summary: Research suggests that multiple members of the histone H1 family play a significant role in chromatin compaction and regulation in human somatic cells. In breast cancer cells, silencing various H1 variants disrupts gene regulation, promotes genome-wide accessibility sites, and activates heterochromatic repeats, triggering an interferon response. This study is the first to simultaneously profile five endogenous H1 variants, providing functional evidence of genome topology alterations upon H1 depletion in human cancer cells.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Ankita Saha, Yamini Dalal
Summary: Histone H1s, a family of chromatin compacting proteins, play essential roles in higher-order chromatin organization. Recent research suggests that different H1 family members have distinct affinities for chromatin and may impact different functions. Advances in technology have improved our understanding of how H1 interacts with chromatin and its importance in epigenetics.
Article
Biochemistry & Molecular Biology
Mitchell A. Ellison, Sanchirmaa Namjilsuren, Margaret K. Shirra, Matthew S. Blacksmith, Rachel A. Schusteff, Eleanor M. Kerr, Fei Fang, Yufei Xiang, Yi Shi, Karen M. Arndt
Summary: The Paf1 complex is a transcription elongation factor that regulates transcription efficiency and impacts RNA synthesis. The subunits Cdc73 and Rtf1 of Paf1C are important for the association with RNA polymerase II on active genes.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Cell Biology
Caojie Liu, Ning Kang, Yuchen Guo, Ping Gong
Summary: CHD proteins play a crucial role in stem cell differentiation and human diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Bo Yuan, Yi Yang, Zhichao Yan, Chun He, Yu H. Sun, Fei Wang, Beibei Wang, Jiamin Shi, Shan Xiao, Fang Wang, Qi Fang, Fei Li, Xinhai Ye, Gongyin Ye
Summary: The linker histone H1 plays a role in folding nucleosomes into a higher-order chromatin structure and has specialized functions in cellular processes. Germline-specific H1 variants have diverse roles in chromatin structure changes during gametogenesis. This study identifies two germline-enriched H1 variants in the testis of the parasitoid wasp Pteromalus puparum and shows their distinct functions in chromatin structure and sperm fertility.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jing Xu, Xiaolu Zhao, Fengbiao Mao, Venkatesha Basrur, Beatrix Ueberheide, Brian T. Chait, C. David Allis, Sean D. Taverna, Shan Gao, Wei Wang, Yifan Liu
Summary: In this study, the EZL1 complex in the protist Tetrahymena thermophila was characterized, revealing its essential role in histone methylation, heterochromatin formation, and genome rearrangement. The interaction between the EZL1 complex and EMA1, as well as PDD1, reinforces its chromatin association and contributes to the dynamic distribution of Polycomb bodies in Tetrahymena development. These findings provide a molecular mechanism linking RNAi and Polycomb repression, ultimately regulating nuclear bodies and genome organization.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Developmental Biology
Aushaq B. Malla, Shannon R. Rainsford, Zachary D. Smith, Bluma J. Lesch
Summary: Unique chromatin remodeling factors regulate nuclear morphology changes during sperm differentiation. Histone-to-protamine exchange is a critical step in this process, and the histone methyltransferase DOT1L plays an essential role in this transition. Loss of DOT1L leads to abnormal sperm head formation and male sterility, due to impaired histone replacement and protamine recruitment. DOT1L also affects transcriptional regulation and gene expression during sperm differentiation.
Article
Biochemical Research Methods
Eva Hoellmueller, Katharina Greiner, Simon M. Kienle, Martin Scheffner, Andreas Marx, Florian Stengel
Summary: Linker histone H1 plays a key role in chromatin organization and maintenance. Using site-specifically mono- and di-acetylated linker histone H1.2 generated by genetic code expansion, this study identified and characterized the acetylation-dependent cellular interactome of H1.2, demonstrating a role in modulating protein-protein interactions. Among the interacting partners identified are translational initiation factors and transcriptional regulators.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Edilene Siqueira, Bo-Hyun Kim, Larry Reser, Robert Chow, Kerry Delaney, Manel Esteller, Mark M. Ross, Jeffrey Shabanowitz, Donald F. Hunt, Sonia Guil, Juan Ausio
Summary: This study used a neural cell line derived from the human ventral mesencephalon, called ReNCell, and its MeCP2 knock out to investigate the changes in linker histones during neural cell differentiation. The results showed that MeCP2 played a crucial role in dendrite and axon development and exhibited extensive co-localization with linker histones. Additionally, the size of the nucleus decreased during differentiation, but the MeCP2 knock out cells showed a significant increase in nucleus size after differentiation.
Article
Biology
Sona Legartova, Gabriela Lochmanova, Eva Bartova
Summary: The study revealed differences in the levels and distribution of phosphorylated histone H1 and H3K9me3 during mitotic phases, and identified ESC-specific phosphorylation sites in a linker histone.
Article
Biochemistry & Molecular Biology
Ryan J. Separovich, Mandy W. M. Wong, Tara K. Bartolec, Joshua J. Hamey, Marc R. Wilkins
Summary: This study comprehensively analyzed the phosphoregulation of the histone methylation network in Saccharomyces cerevisiae. The functional investigation revealed the important roles of phosphorylation sites on several enzymes in cellular stress responses.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Mattia Zaghi, Federica Banfi, Luca Massimino, Monica Volpin, Edoardo Bellini, Simone Brusco, Ivan Merelli, Cristiana Barone, Michela Bruni, Linda Bossini, Luigi Antonio Lamparelli, Laura Pintado, Deborah D'Aliberti, Silvia Spinelli, Luca Mologni, Gaia Colasante, Federica Ungaro, Jean-Michel Cioni, Emanuele Azzoni, Rocco Piazza, Eugenio Montini, Vania Broccoli, Alessandro Sessa
Summary: Histone acetylation, regulated by the oncoprotein SET, plays a critical role in modulating gene transcription within enhancers. Disruption of this regulation is associated with developmental disorders.
NATURE COMMUNICATIONS
(2023)
Article
Virology
Gary Z. Wang, Stephen P. Goff
Summary: This study reveals the essential role of p12 protein in tethering viral DNA to host chromatin to allow loading of histones onto the viral DNA. Mutants lacking tethering activity fail to acquire histones, retain capsid and nucleocapsid proteins, and are poorly transcribed, defining a new requirement for a viral protein in chromatinization of viral DNA.
JOURNAL OF VIROLOGY
(2021)
Article
Chemistry, Medicinal
Isabelle A. Engelberg, Jiuyang Liu, Jacqueline L. Norris-Drouin, Stephanie H. Cholensky, Samantha A. Ottavi, Stephen Frye, Tatiana G. Kutateladze, Lindsey James
Summary: PHF1, an accessory component of polycomb repressive complex 2, recognizes the active chromatin mark H3K36me3 for transcriptional regulation. UNC6641 is a peptidomimetic antagonist of PHF1 Tudor domain, capable of binding both PHF1 and PHF19 with high potency, providing insights into the binding mechanism through crystal structure and other data. Additionally, UNC6641 facilitates the development of a high-throughput assay for identifying small molecule binders of PHF1.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Xiao-dong Sun, Xing-juan Shi, Xiao-ou Sun, You-guang Luo, Xiao-jing Wu, Chang-fu Yao, Hai-yang Yu, Deng-wen Li, Min Liu, Jun Zhou
ACTA PHARMACOLOGICA SINICA
(2011)
Article
Biochemistry & Molecular Biology
Kristen M. Johansen, Arthur Forer, Changfu Yao, Jack Girton, Jorgen Johansen
CHROMOSOME RESEARCH
(2011)
Article
Biochemistry & Molecular Biology
Chao Wang, Weili Cai, Yeran Li, Jack Girton, Jorgen Johansen, Kristen M. Johansen
Article
Genetics & Heredity
Huai Deng, Weili Cai, Chao Wang, Stephanie Lerach, Marion Delattre, Jack Girton, Jorgen Johansen, Kristen M. Johansen
Article
Cell Biology
Chao Wang, Weili Cai, Yeran Li, Huai Deng, Xiaomin Bao, Jack Girton, Jorgen Johansen, Kristen M. Johansen
JOURNAL OF CELL SCIENCE
(2011)
Article
Multidisciplinary Sciences
Joern Boeke, Catherine Regnard, Weili Cai, Jorgen Johansen, Kristen M. Johansen, Peter B. Becker, Axel Imhof
Article
Cell Biology
Myreille Larouche, David Kachaner, Peng Wang, Karine Normandin, Damien Garrido, Changfu Yao, Maxime Cormier, Kristen M. Johansen, Jorgen Johansen, Vincent Archambault
Summary: Mitotic entry involves the inhibition of PP2A-B55/Tws, which is induced by Greatwall phosphorylation of Endos. The correct localization and phosphorylation of Tws and Endos play essential roles in mitotic regulation. The spatiotemporal regulation of Endos by Greatwall is conserved in humans and disruptions lead to mitotic defects.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Apoorva Mulay, Bindu Konda, Gustavo Garcia, Changfu Yao, Stephen Beil, Jaquelyn M. Villalba, Colin Koziol, Chandani Sen, Arunima Purkayastha, Jay K. Kolls, Derek A. Pociask, Patrizia Pessina, Julio Sainz de Aja, Carolina Garcia-de-Alba, Carla F. Kim, Brigitte Gomperts, Vaithilingaraja Arumugaswami, Barry R. Stripp
Summary: This study established primary human lung epithelial infection models to investigate the initial responses of proximal and distal lung epithelium to SARS-CoV-2 infection. The findings showed that epithelial cells in different areas of the lungs are susceptible to SARS-CoV-2 infection, leading to a cell-autonomous proinflammatory response, with remdesivir proving effective in suppressing viral infection and replication.
Article
Multidisciplinary Sciences
Ting Xie, Vrishika Kulur, Ningshan Liu, Nan Deng, Yizhou Wang, Simon Coyle Rowan, Changfu Yao, Guanling Huang, Xue Liu, Forough Taghavifar, Jiurong Liang, Cory Hogaboam, Barry Stripp, Peter Chen, Dianhua Jiang, Paul W. Noble
Summary: Recent studies have shown that impaired renewal of type 2 alveolar epithelial cells (ATII) in IPF patients and mice with defective ATII can lead to severe pulmonary fibrosis. Growth hormone receptor (GHR) expression, mainly found in mesenchymal cells, is significantly decreased in IPF lungs, but higher levels of GHR expression are associated with better lung function in IPF patients. The findings suggest that a previously unidentified mesenchymal paracrine signaling via GHR can support ATII progenitor cell renewal and limit the severity of lung fibrosis.
Article
Immunology
Xue Liu, Yan Geng, Jiurong Liang, Ana Lucia Coelho, Changfu Yao, Nan Deng, Yizhou Wang, Kristy Dai, Guanling Huang, Ting Xie, Ningshan Liu, Simon C. Rowan, Forough Taghavifar, Vrishika Kulur, Zhenqiu Liu, Barry R. Stripp, Cory M. Hogaboam, Dianhua Jiang, Paul W. Noble
Summary: This study suggests that HER2 signaling may play a crucial role in fibroblast invasion and lung fibrosis in IPF, making it a potential target for therapeutic intervention.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Konstantinos-Dionysios Alysandratos, Carolina Garcia-de-Alba, Changfu Yao, Patrizia Pessina, Jessie Huang, Carlos Villacorta-Martin, Olivia T. Hix, Kasey Minakin, Claire L. Burgess, Pushpinder Bawa, Aditi Murthy, Bindu Konda, Michael F. Beers, Barry R. Stripp, Carla F. Kim, Darrell N. Kotton
Summary: This study compared the transcriptomes of primary adult human AEC2s, their cultured progeny, and human induced pluripotent stem cell-derived AEC2s, and found that each population has a distinct transcriptomic space, with cultured AEC2s showing similarities and differences from freshly purified cells. The study also discovered an inverse relationship between proliferative and maturation states across each cell type. Additionally, it was found that cultures of both types of human AEC2s did not generate alveolar type 1 cells, but a subset of induced pluripotent stem cell-derived AEC2s acquired a transitional cell state when co-cultured with fibroblasts.
Article
Medicine, Research & Experimental
Jiurong Liang, Guanling Huang, Xue Liu, Forough Taghavifar, Ningshan Liu, Yizhou Wang, Nan Deng, Changfu Yao, Ting Xie, Vrishika Kulur, Kristy Dai, Ankita Burman, Simon C. Rowan, S. Samuel Weigt, John Belperio, Barry Stripp, William C. Parks, Dianhua Jiang, Paul W. Noble
Summary: This study identified a deficiency of the zinc transporter SLC39A8 (ZIP8) in Type 2 alveolar epithelial cells (AEC2s) from both idiopathic pulmonary fibrosis (IPF) lungs and lungs of old mice, which is associated with impaired AEC2 renewal capacity and enhanced lung fibrosis. The regulation of AEC2 progenitor function by ZIP8 is dependent on SIRT1. Replenishment with exogenous zinc and activation of SIRT1 promote self-renewal and differentiation of AEC2s, and therapeutic strategies targeting zinc metabolism and SIRT1 signaling could potentially improve AEC2 progenitor function and mitigate fibrogenesis.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Medicine, Research & Experimental
Tanyalak Parimon, Changfu Yao, David M. Habiel, Lingyin Ge, Stephanie A. Bora, Rena Brauer, Christopher M. Evans, Ting Xie, Felix Alonso-Valenteen, Lali K. Medina-Kauwe, Dianhua Jiang, Paul W. Noble, Cory M. Hogaboam, Nan Deng, Olivier Burgy, Travis J. Antes, Melanie Konigshoff, Barry R. Stripp, Sina A. Gharib, Peter Chen