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C. David Allis

Xiaozhe Xiong, Tatyana Panchenko, Shuang Yang, Shuai Zhao, Peiqiang Yan, Wenhao Zhang, Wei Xie, Yuanyuan Li, Yingming Zhao, C David Allis, Haitao Li
Recognition of histone covalent modifications by 'reader' modules constitutes a major mechanism for epigenetic regulation. A recent upsurge of newly discovered histone lysine acylations, such as crotonylation (Kcr), butyrylation (Kbu), and propionylation (Kpr), greatly expands the coding potential of histone lysine modifications. Here we demonstrate that the histone acetylation-binding double PHD finger (DPF) domains of human MOZ (also known as KAT6A) and DPF2 (also known as BAF45d) accommodate a wide range of histone lysine acylations with the strongest preference for Kcr...
October 24, 2016: Nature Chemical Biology
Steven Z Josefowicz, Miho Shimada, Anja Armache, Charles H Li, Rand M Miller, Shu Lin, Aerin Yang, Brian D Dill, Henrik Molina, Hee-Sung Park, Benjamin A Garcia, Jack Taunton, Robert G Roeder, C David Allis
The inflammatory response requires coordinated activation of both transcription factors and chromatin to induce transcription for defense against pathogens and environmental insults. We sought to elucidate the connections between inflammatory signaling pathways and chromatin through genomic footprinting of kinase activity and unbiased identification of prominent histone phosphorylation events. We identified H3 serine 28 phosphorylation (H3S28ph) as the principal stimulation-dependent histone modification and observed its enrichment at induced genes in mouse macrophages stimulated with bacterial lipopolysaccharide...
October 20, 2016: Molecular Cell
Charles Boelen, David Pearson, Arthur Kaufman, James Rourke, Robert Woollard, David C Marsh, Trevor Gibbs
Health systems worldwide are confronted with challenges due to increased demand from their citizens, an aging population, a variety of health risks and limited resources. Key health stakeholders, including academic institutions and medical schools, are urged to develop a common vision for a more efficient and equitable health sector. It is in this environment that Boelen and Heck defined the concept of the "Social Accountability of Medical Schools" - a concept that encourages schools to produce not just highly competent professionals, but professionals who are equipped to respond to the changing challenges of healthcare through re-orientation of their education, research and service commitments, and be capable of demonstrating a positive effect upon the communities they serve...
September 9, 2016: Medical Teacher
Ben Antebi, Avi Benov, Elizabeth A Mann-Salinas, Tuan D Le, Leopoldo C Cancio, Joseph C Wenke, Haim Paran, Avraham Yitzhak, Bader Tarif, Kirby R Gross, David Dagan, Elon Glassberg
BACKGROUND: As new conflicts emerge and enemies evolve, military medical organizations worldwide must adopt the "lessons learned." In this study, we describe roles of care (ROCs) deployed and injuries sustained by both US and Israeli militaries during recent conflicts. The purpose of this collaborative work is facilitate exchange of medical data among allied forces in order to advance military medicine and facilitate strategic readiness for future military engagements that may involve less predictable situations of evacuation and care, such as prolonged field care...
November 2016: Journal of Trauma and Acute Care Surgery
David Olusoga Ogbolu, Armstrong Oyebode Alli, Michael C Anorue, Oluwole Adebayo Daini, Afolabi Oluwadun
BACKGROUND: Until recently, mechanisms of resistance to quinolones in Gram-negative bacteria were believed to be only chromosome encoded. However, emergence of plasmid-mediated quinolone resistance (PMQR) has been reported worldwide. AIM: This study investigated distribution of PMQR in Gram-negative bacteria from a tertiary hospital in eastern part of Nigeria. MATERIALS AND METHODS: Seventy-one nonduplicate Gram-negative bacterial isolates of eight species were analyzed for antimicrobial susceptibility, genotypic detection of various PMQRs, typed by random amplified polymorphic DNA (RAPD) and analysis of plasmids present, including replicon typing...
July 2016: Indian Journal of Pathology & Microbiology
Diane M Damez-Werno, HaoSheng Sun, Kimberly N Scobie, Ningyi Shao, Jaclyn Rabkin, Caroline Dias, Erin S Calipari, Ian Maze, Catherine J Pena, Deena M Walker, Michael E Cahill, Ramesh Chandra, Amy Gancarz, Ezekiell Mouzon, Joseph A Landry, Hannah Cates, Mary-Kay Lobo, David Dietz, C David Allis, Ernesto Guccione, Gustavo Turecki, Paola Defilippi, Rachael L Neve, Yasmin L Hurd, Li Shen, Eric J Nestler
Repeated cocaine exposure regulates transcriptional regulation within the nucleus accumbens (NAc), and epigenetic mechanisms-such as histone acetylation and methylation on Lys residues-have been linked to these lasting actions of cocaine. In contrast to Lys methylation, the role of histone Arg (R) methylation remains underexplored in addiction models. Here we show that protein-R-methyltransferase-6 (PRMT6) and its associated histone mark, asymmetric dimethylation of R2 on histone H3 (H3R2me2a), are decreased in the NAc of mice and rats after repeated cocaine exposure, including self-administration, and in the NAc of cocaine-addicted humans...
August 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
Shuang Yang, Xiangdong Zheng, Chao Lu, Guo-Min Li, C David Allis, Haitao Li
High-frequency point mutations of genes encoding histones have been identified recently as novel drivers in a number of tumors. Specifically, the H3K36M/I mutations were shown to be oncogenic in chondroblastomas and undifferentiated sarcomas by inhibiting H3K36 methyltransferases, including SETD2. Here we report the crystal structures of the SETD2 catalytic domain bound to H3K36M or H3K36I peptides with SAH (S-adenosylhomocysteine). In the complex structure, the catalytic domain adopts an open conformation, with the K36M/I peptide snuggly positioned in a newly formed substrate channel...
July 15, 2016: Genes & Development
Giovanni Gambaro, Emanuele Croppi, Fredric Coe, James Lingeman, Orson Moe, Elen Worcester, Noor Buchholz, David Bushinsky, Gary C Curhan, Pietro Manuel Ferraro, Daniel Fuster, David S Goldfarb, Ita Pfeferman Heilberg, Bernard Hess, John Lieske, Martino Marangella, Dawn Milliner, Glen M Preminger, Jose' Manuel Reis Santos, Khashayar Sakhaee, Kemal Sarica, Roswitha Siener, Pasquale Strazzullo, James C Williams
BACKGROUND: Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research. DESIGN: A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information...
July 25, 2016: Journal of Nephrology
David Olusoga Ogbolu, Oyebode Terry Alli, Itunu Odeleye, Adeolu S Oluremi
OBJECTIVE: To determine the prevalence of viral haemoparasites in prospective Nigerian blood donors. METHODS: Ethical clearance was obtained and informed consent questionnaires were distributed to blood donors to obtain their demographical data. A total of 186 blood donors from LAUTECH Teaching Hospital, Osogbo were tested for hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) using rapid test kit and enzyme linked immunosorbent assay. RESULTS: The highest prevalence of blood transmitted infections was 182 (97...
July 2016: Asian Pacific Journal of Tropical Medicine
Ally Olotu, Gregory Fegan, Juliana Wambua, George Nyangweso, Amanda Leach, Marc Lievens, David C Kaslow, Patricia Njuguna, Kevin Marsh, Philip Bejon
BACKGROUND: The candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. METHODS: We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS,S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of >2500 parasites per cubic millimeter)...
June 30, 2016: New England Journal of Medicine
C David Allis, Thomas Jenuwein
Over the past 20 years, breakthrough discoveries of chromatin-modifying enzymes and associated mechanisms that alter chromatin in response to physiological or pathological signals have transformed our knowledge of epigenetics from a collection of curious biological phenomena to a functionally dissected research field. Here, we provide a personal perspective on the development of epigenetics, from its historical origins to what we define as 'the modern era of epigenetic research'. We primarily highlight key molecular mechanisms of and conceptual advances in epigenetic control that have changed our understanding of normal and perturbed development...
August 2016: Nature Reviews. Genetics
Alex C DiBartola, Joshua S Everhart, Christopher C Kaeding, Robert A Magnussen, David C Flanigan
BACKGROUND: The objective of this study was to systematically evaluate the existing literature to compare the biomechanical effects of low dose and high dose gamma irradiation on commonly used ACL allografts. METHODS: A systematic search was performed in PubMed, Cumulative Index for Nursing and Allied Health Literature (CINAHL), Cochrane Reviews, SCOPUS, and SportDiscus. Nine studies were identified that met the following inclusion criteria: 1) controlled laboratory study, 2) investigation of standard allografts for anterior cruciate ligament reconstruction (ACLR), 3) gamma irradiation (dose reported) and a negative control group, and 4) mechanical loading (results reported)...
October 2016: Knee
Alexey A Soshnev, Steven Z Josefowicz, C David Allis
Information encoded in DNA is interpreted, modified, and propagated as chromatin. The diversity of inputs encountered by eukaryotic genomes demands a matching capacity for transcriptional outcomes provided by the combinatorial and dynamic nature of epigenetic processes. Advances in genome editing, visualization technology, and genome-wide analyses have revealed unprecedented complexity of chromatin pathways, offering explanations to long-standing questions and presenting new challenges. Here, we review recent findings, exemplified by the emerging understanding of crossregulatory interactions within chromatin, and emphasize the pathologic outcomes of epigenetic misregulation in cancer...
June 2, 2016: Molecular Cell
Bronwynne C Evans, David W Coon, Michael J Belyea
This mixed methods, multi-site, National Institute of Nursing Research (NINR)-funded, interdisciplinary, descriptive study aimed to identify expressions of worry in qualitative data obtained from caregiving Mexican American (MA) families assisting older adults. The purpose of this portion of the inquiry was to determine how worry is expressed, what happens to caregivers when they worry, and what adaptive strategies they used. We examined semi-structured interviews completed during six in-home visits with 116 caregivers...
August 2014: Hispanic Journal of Behavioral Sciences
Hariharan Jayaram, Dominik Hoelper, Siddhant U Jain, Nico Cantone, Stefan M Lundgren, Florence Poy, C David Allis, Richard Cummings, Steven Bellon, Peter W Lewis
Lysine to methionine (K-to-M) mutations in genes encoding histone H3 are thought to drive a subset of pediatric brain and bone cancers. These high-frequency K-to-M mutations occur at sites of methylation on histone H3, and tumors containing the mutant histones exhibit a global loss of specific histone methylation marks. Previous studies showed that K-to-M mutant histones, also known as oncohistones, are potent orthosteric inhibitors of specific Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain methyltransferases...
May 31, 2016: Proceedings of the National Academy of Sciences of the United States of America
Chao Lu, Siddhant U Jain, Dominik Hoelper, Denise Bechet, Rosalynn C Molden, Leili Ran, Devan Murphy, Sriram Venneti, Meera Hameed, Bruce R Pawel, Jay S Wunder, Brendan C Dickson, Stefan M Lundgren, Krupa S Jani, Nicolas De Jay, Simon Papillon-Cavanagh, Irene L Andrulis, Sarah L Sawyer, David Grynspan, Robert E Turcotte, Javad Nadaf, Somayyeh Fahiminiyah, Tom W Muir, Jacek Majewski, Craig B Thompson, Ping Chi, Benjamin A Garcia, C David Allis, Nada Jabado, Peter W Lewis
Several types of pediatric cancers reportedly contain high-frequency missense mutations in histone H3, yet the underlying oncogenic mechanism remains poorly characterized. Here we report that the H3 lysine 36-to-methionine (H3K36M) mutation impairs the differentiation of mesenchymal progenitor cells and generates undifferentiated sarcoma in vivo. H3K36M mutant nucleosomes inhibit the enzymatic activities of several H3K36 methyltransferases. Depleting H3K36 methyltransferases, or expressing an H3K36I mutant that similarly inhibits H3K36 methylation, is sufficient to phenocopy the H3K36M mutation...
May 13, 2016: Science
Ying Liu, Eugenia G Giannopoulou, Duancheng Wen, Ilaria Falciatori, Olivier Elemento, C David Allis, Shahin Rafii, Marco Seandel
Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin...
2016: Nature Communications
Yuanyuan Li, Benjamin R Sabari, Tatyana Panchenko, Hong Wen, Dan Zhao, Haipeng Guan, Liling Wan, He Huang, Zhanyun Tang, Yingming Zhao, Robert G Roeder, Xiaobing Shi, C David Allis, Haitao Li
Recognition of histone covalent modifications by chromatin-binding protein modules ("readers") constitutes a major mechanism for epigenetic regulation, typified by bromodomains that bind acetyllysine. Non-acetyl histone lysine acylations (e.g., crotonylation, butyrylation, propionylation) have been recently identified, but readers that prefer these acylations have not been characterized. Here we report that the AF9 YEATS domain displays selectively higher binding affinity for crotonyllysine over acetyllysine...
April 21, 2016: Molecular Cell
Dan Zhao, Haipeng Guan, Shuai Zhao, Wenyi Mi, Hong Wen, Yuanyuan Li, Yingming Zhao, C David Allis, Xiaobing Shi, Haitao Li
No abstract text is available yet for this article.
May 2016: Cell Research
S R F Meneses, A P Goode, A E Nelson, J Lin, J M Jordan, K D Allen, K L Bennell, L S Lohmander, L Fernandes, M C Hochberg, M Underwood, P G Conaghan, S Liu, T E McAlindon, Y M Golightly, D J Hunter
BACKGROUND: Numerous scientific organisations have developed evidence-based recommendations aiming to optimise the management of osteoarthritis (OA). Uptake, however, has been suboptimal. The purpose of this exercise was to harmonize the recent recommendations and develop a user-friendly treatment algorithm to facilitate translation of evidence into practice. METHODS: We updated a previous systematic review on clinical practice guidelines (CPGs) for OA management...
September 2016: Osteoarthritis and Cartilage
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