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Histone modification

Man Liu, Jingying Zhou, Zhiwei Chen, Alfred Sze-Lok Cheng
The tumour microenvironment plays an instrumental role in cancer development, progression and treatment response/resistance. Accumulating evidence underscores the fundamental importance of epigenetic regulation in tumour immune evasion. Following many pioneering discoveries demonstrating malignant transformation through epigenetic anomalies ("epimutations"), there is also growing emphasis on elucidating aberrant epigenetic mechanisms that reprogramme the milieu of tumour-associated immune and stromal cells toward an immunosuppressive state...
October 22, 2016: Journal of Pathology
Martine Boccara, Alexis Sarazin, Bernard Billoud, Agnes Bulski, Louise Chapell, David Baulcombe, Vincent Colot
Epigenetic response to stress in plants involves changes in DNA methylation, histone modifications, and expression of small noncoding RNAs (sRNA). Here we present the method of analysis of differential expression of sRNA populations using DNA tiling arrays. sRNA extracted from Arabidopsis thaliana plants exposed to pathogen elicitor or control plants were reverse-transcribed into cDNAs, and subsequently hybridized after labeling to a custom-made DNA tiling array covering Arabidopsis chromosome 4. We first designed a control experiment with eight cDNA clones corresponding to sequences located on chromosome 4 and obtained robust and specific hybridization signals...
2017: Methods in Molecular Biology
Julia Engelhorn, Franziska Turck
Genome-wide analyses of chromatin factor-binding sites or histone modification localization generate lists of up to several thousand potential target genes. For many model organisms, large annotation databases are available to help with the characterization and classification of genomic datasets. The term meta-analysis has been coined for this type of multi-database comparison. In this chapter, we describe a workflow to perform a transcriptional and functional analysis of genome-wide target genes. Sources of transcription data and clustering tools to subdivide genes according to their expression pattern are described...
2017: Methods in Molecular Biology
Wanhui You, Stéphane Pien, Ueli Grossniklaus
Epigenetic control of plant development via histone modifications is involved in different processes ranging from embryonic development, vegetative development, flowering time control, floral organ development, to pollen tube growth. The identification of an increasing number of epigenetically regulated processes was greatly advanced by methods allowing the survey of genome-wide histone modifications and chromatin-protein interactions. However, genome-wide approaches are too broad to access in detail a large number of histone modifications taking place at a single locus...
2017: Methods in Molecular Biology
Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
Deepika Jaiswal, Rashi Turniansky, Erin M Green
When yeast cells are challenged by a fluctuating environment, signaling networks activate differentiation programs that promote their individual or collective survival. These programs include the initiation of meiotic sporulation, the formation of filamentous growth structures, and the activation of programmed cell death pathways. The establishment and maintenance of these distinct cell fates are driven by massive gene expression programs that promote the necessary changes in morphology and physiology. While these genomic reprogramming events depend on a specialized network of transcription factors, a diverse set of chromatin regulators, including histone-modifying enzymes, chromatin remodelers, and histone variants, also play essential roles...
October 18, 2016: Journal of Molecular Biology
Srikanth Appikonda, Kaushik N Thakkar, Michelle Craig Barton
Tripartite Motif-containing protein 24 (TRIM24) functions as an E3 ligase targeting p53 for ubiquitination, a histone 'reader' that interacts with a specific signature of histone post-translational modifications and a co-regulator of nuclear receptor-regulated transcription. Although mouse models of Trim24 depletion suggest that TRIM24 may be a liver-specific tumor suppressor, several studies show that human TRIM24 is an oncogene when aberrantly over expressed. This review focuses on the mechanisms of TRIM24 functions in oncogenesis and metabolic reprogramming, which underlie recent interest in therapeutic targeting of aberrant TRIM24 in human cancers...
March 2016: Drug Discovery Today. Technologies
Srimoyee Ghosh, Jose M Lora
Epigenetic control of gene expression is enforced in part through histone modifications. Bromodomain and extra terminal domain (BET) proteins function as crucial chromatin readers, responsible for interpretation of the chromatin code in diverse cellular contexts, ultimately impacting gene transcription. BET proteins can play a major role in inflammation by profoundly affecting the biology of the Thelper 17 (TH17) lineage. We summarize recent studies focusing on BET inhibition as a viable therapeutic alternative for the control of autoimmune diseases driven by aberrant activation of TH17 cells...
March 2016: Drug Discovery Today. Technologies
Anna Chung-Kwan Tse, Jing-Woei Li, Simon Yuan Wang, Ting-Fung Chan, Keng Po Lai, Rudolf Shiu-Sun Wu
Hypoxia is a global environmental concern and poses a significant threat to aquatic ecosystems, including the sustainability of natural fish populations. The deleterious effects of hypoxia on fish reproductive fitness, as mediated by disruption of sex hormones and gene expression along the Brain-Pituitary-Gonad axis, have been well documented. Recently, we further demonstrated that the observed disruption of steroidogenesis in the ovary of marine medaka Oryzias melastigma is mediated through microRNAs (miRNAs)...
October 8, 2016: Aquatic Toxicology
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
Paule V Joseph, Sarah K Abey, Wendy A Henderson
Nutrition is a factor involved in inflammation and a modulator of risk toward some cancers, and the complexity of linkages between dietary components and epigenetics mechanisms (e.g., DNA methylation, histone modification, chromatin remodeling) may affect the inflammation phenotype and the development of cancer. An increasing number of studies support the role of diet in cancer development, prevention, and treatment. Although current knowledge regarding nutri-epigenetics is expanding, more work is needed, and nurse scientists have the potential to significantly contribute to the expansion of this knowledge...
November 1, 2016: Oncology Nursing Forum
Gianluigi Franci, Federica Sarno, Angela Nebbioso, Lucia Altucci
Epigenetic modifications are functionally involved in gene expression regulation. In particular, histone posttranslational modifications play a crucial role in functional chromatin organization. Several drugs able to inhibit or stimulate some families of proteins involved in epigenetic histone regulation have been found, a number of which are FDA-approved for the treatment of cutaneous T-cell lymphoma or are in phase I/II/III clinical trials for solid tumors. Although some protein families, such as histone deacetylases and their inhibitors, are well characterized, our understanding of histone lysine demethylases is still incomplete...
October 21, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Nicole Mons, Daniel Beracochea
A prime mechanism that contributes to the development and maintenance of alcoholism is the dysregulation of the hypothalamic-pituitary-adrenal axis activity and the release of glucocorticoids (cortisol in humans and primates, corticosterone in rodents) from the adrenal glands. In the brain, sustained, local elevation of glucocorticoid concentration even long after cessation of chronic alcohol consumption compromises functional integrity of a circuit, including the prefrontal cortex (PFC), the hippocampus (HPC), and the amygdala (AMG)...
2016: Frontiers in Psychiatry
Caitlin G Howe, Xinhua Liu, Megan N Hall, Vesna Ilievski, Marie A Caudill, Olga Malysheva, Angela M Lomax-Luu, Faruque Parvez, Abu B Siddique, Hasan Shahriar, Mohammad N Uddin, Tariqul Islam, Joseph H Graziano, Max Costa, Mary V Gamble
BACKGROUND: Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation. METHODS: We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMCs) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults...
October 20, 2016: Cancer Epidemiology, Biomarkers & Prevention
Demin Cai, Mengjie Yuan, Haoyu Liu, Shifeng Pan, Wenqiang Ma, Jian Hong, Ruqian Zhao
Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets...
October 18, 2016: Nutrients
Inderjeet Kaur, Mohammad Zeeshan, Ekta Saini, Abhinav Kaushik, Asif Mohmmed, Dinesh Gupta, Pawan Malhotra
Post-transcriptional and post-translational modifications play a major role in Plasmodium life cycle regulation. Lysine methylation of histone proteins is well documented in several organisms, however in recent years lysine methylation of proteins outside histone code is emerging out as an important post-translational modification (PTM). In the present study we have performed global analysis of lysine methylation of proteins in asexual blood stages of Plasmodium falciparum development. We immunoprecipitated stage specific Plasmodium lysates using anti-methyl lysine specific antibodies that immunostained the asexual blood stage parasites...
October 20, 2016: Scientific Reports
Adil El Taghdouini, Leo A van Grunsven
Chronic liver injury to hepatocytes or cholangiocytes, when left unmanaged, leads to the development of liver fibrosis, a condition characterized by the excessive intrahepatic deposition of extracellular matrix proteins. Activated hepatic stellate cells constitute the predominant source of extracellular matrix in fibrotic livers and their transition from a quiescent state during fibrogenesis is associated with important alterations in their transcriptional and epigenetic landscape. Areas covered: We briefly describe the processes involved in hepatic stellate cell activation and discuss our current understanding of alterations in the epigenetic landscape, i...
October 20, 2016: Expert Review of Gastroenterology & Hepatology
Mandy Beyer, Nicole Kiweler, Siavosh Mahboobi, Oliver H Krämer
Histone deacetylases (HDACs) catalyze the deacetylation of lysine residues in their target proteins. This biochemical modification can have profound effects on the functions of these proteins and a dysregulation of HDAC activity contributes to severe diseases, including neoplastic transformation. In the following chapter, we present a strategy that allows to distinguish between the inhibition of the class I HDACs HDAC1, 2, and 3 and of the class IIb HDAC HDAC6. This method is based on Western blot and relies on the detection of hyperacetylated substrates of class I or class IIb HDACs in lysates from cells that were treated with histone deacetylase inhibitors (HDACi)...
2017: Methods in Molecular Biology
Tobias Wagner, Maren Godmann, Thorsten Heinzel
Histone deacetylases (HDACs) are controlling dynamic protein acetylation by removing acetyl moieties from lysine. Histone deacetylases themselves are regulated on the posttranslational level, including modifications with small ubiquitin-like modifier (SUMO) proteins. Detecting SUMO modifications of deacetylases by immunoblotting is technically challenging due to the typically low ratio of the modified compared to the unmodified species. Here, we describe a set of methods for the detection of endogenous sumoylated HDACs by immunoprecipitation and immunoblotting techniques...
2017: Methods in Molecular Biology
Sophia Pinz, Anne Rascle
Transcriptional activation by STAT5 is repressed by deacetylase inhibitors. Investigating the role of deacetylases (HDACs) in STAT5-mediated transcription implies the analysis of molecular events taking place at the chromatin level. We describe here two alternative methods of chromatin immunoprecipitation that allow the characterization of chromatin modifications ensuing STAT5 activation and its inhibition by deacetylase inhibitors, in particular changes in histone acetylation, in histone occupancy, and in the association/dissociation of transcription factors and other chromatin-associated factors...
2017: Methods in Molecular Biology
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