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histone modification chromatin cancer

Graziela de Sá Machado Araújo, Ronaldo da Silva Francisco Junior, Cristina Dos Santos Ferreira, Pedro Thyago Mozer Rodrigues, Douglas Terra Machado, Thais Louvain de Souza, Jozimara Teixeira de Souza, Cleiton Figueiredo Osorio da Silva, Antônio Francisco Alves da Silva, Claudia Caixeta Franco Andrade, Alan Tardin da Silva, Victor Ramos, Ana Beatriz Garcia, Filipe Brum Machado, Enrique Medina-Acosta
A hallmark of imprinted genes in mammals is the occurrence of parent-of-origin-dependent asymmetry of DNA cytosine methylation (5m C) of alleles at CpG islands (CGIs) in their promoter regions. This 5m CpG asymmetry between the parental alleles creates allele-specific imprinted differentially methylated regions (iDMRs). iDMRs are often coupled to the transcriptional repression of the methylated allele and the activation of the unmethylated allele in a tissue-specific, developmental-stage-specific and/or isoform-specific fashion...
2018: Frontiers in Genetics
Emily C Sheppard, Rikke Brandstrup Morrish, Michael J Dillon, Rebecca Leyland, Richard Chahwan
Epigenetic modifications, such as histone modifications, DNA methylation status, and non-coding RNAs (ncRNA), all contribute to antibody maturation during somatic hypermutation (SHM) and class-switch recombination (CSR). Histone modifications alter the chromatin landscape and, together with DNA primary and tertiary structures, they help recruit Activation-Induced Cytidine Deaminase (AID) to the immunoglobulin (Ig) locus. AID is a potent DNA mutator, which catalyzes cytosine-to-uracil deamination on single-stranded DNA to create U:G mismatches...
2018: Frontiers in Immunology
Kyle T Householder, Danielle M DiPerna, Eugene P Chung, Anne Rosa Luning, Duong T Nguyen, Sarah E Stabenfeldt, Shwetal Mehta, Rachael W Sirianni
Histone deacetylases (HDACs) are known to be key enzymes in cancer development and progression through their modulation of chromatin structure and the expression and post-translational modification of numerous proteins. Aggressive dedifferentiated tumors, like glioblastoma, frequently overexpress HDACs, while HDAC inhibition can lead to cell cycle arrest, promote cellular differentiation and induce apoptosis. Although multiple HDAC inhibitors, such as quisinostat, are of interest in oncology due to their potent in vitro efficacy, their failure in the clinic as monotherapies against solid tumors has been attributed to poor delivery...
February 24, 2018: Colloids and Surfaces. B, Biointerfaces
Linbo Gao, David Cheng, Jie Yang, Renyi Wu, Wenji Li, Ah-Ng Kong
Increasing evidence suggests that epigenetic aberrations contribute to the development and progression of cancers such as lung cancer. The promoter region of miR-9-3 was recently found to be hypermethylated in lung cancer, resulting in down-regulation of miR-9-3 and poor patient prognosis. Sulforaphane (SFN), a natural compound that is obtained from cruciferous vegetables, has potent anticancer activities. In this study, we aimed to investigate the effect of SFN on restoring the miR-9-3 level in lung cancer A549 cells through epigenetic regulation...
February 9, 2018: Journal of Nutritional Biochemistry
Srikanth Appikonda, Kaushik N Thakkar, Parantu K Shah, Sharon Y R Dent, Jannik N Andersen, Michelle Craig Barton
Proteins with domains that recognize and bind post-translational modifications (PTMs) of histones are collectively termed epigenetic readers. Numerous interactions between specific reader protein domains and histone PTMs and their regulatory outcomes have been reported, but little is known about how reader proteins may in turn be modulated by these interactions. Tripartite motif-containing protein 24 (TRIM24) is a histone reader aberrantly expressed in multiple cancers. Here, our investigation revealed functional crosstalk between histone acetylation and TRIM24 SUMOylation...
March 9, 2018: Journal of Biological Chemistry
Johayra Simithy, Simone Sidoli, Benjamin A Garcia
The chromatin fiber is the control panel of eukaryotic cells. Chromatin is mostly composed of DNA, which contains the genetic instruction for cell phenotype, and histone proteins, which provide the scaffold for chromatin folding and part of the epigenetic inheritance. Histone writers/erasers "flag" chromatin regions by catalyzing/removing covalent histone post-translational modifications (PTMs). Histone PTMs chemically contribute to chromatin relaxation or compaction and recruit histone readers to modulate DNA readout...
March 7, 2018: Proteomics
Zhenghao Li, Hisanori Takenobu, Amallia Nuggetsiana Setyawati, Nobuhiro Akita, Masayuki Haruta, Shunpei Satoh, Yoshitaka Shinno, Koji Chikaraishi, Kyosuke Mukae, Jesmin Akter, Ryuichi P Sugino, Atsuko Nakazawa, Akira Nakagawara, Hiroyuki Aburatani, Miki Ohira, Takehiko Kamijo
The polycomb repressor complex 2 molecule EZH2 is now known to play a role in essential cellular processes, namely, cell fate decisions, cell cycle regulation, senescence, cell differentiation, and cancer development/progression. EZH2 inhibitors have recently been developed; however, their effectiveness and underlying molecular mechanisms in many malignancies have not yet been elucidated in detail. Although the functional role of EZH2 in tumorigenesis in neuroblastoma (NB) has been investigated, mutations of EZH2 have not been reported...
March 6, 2018: Oncogene
Raúl F Pérez, Juan Ramón Tejedor, Gustavo F Bayón, Agustín F Fernández, Mario F Fraga
Cancer is an aging-associated disease, but the underlying molecular links between these processes are still largely unknown. Gene promoters that become hypermethylated in aging and cancer share a common chromatin signature in ES cells. In addition, there is also global DNA hypomethylation in both processes. However, the similarity of the regions where this loss of DNA methylation occurs is currently not well characterized, and it is unknown if such regions also share a common chromatin signature in aging and cancer...
March 5, 2018: Aging Cell
David Corujo, Marcus Buschbeck
Histone variants are chromatin components that replace replication-coupled histones in a fraction of nucleosomes and confer particular characteristics to chromatin. H2A variants represent the most numerous and diverse group among histone protein families. In the nucleosomal structure, H2A-H2B dimers can be removed and exchanged more easily than the stable H3-H4 core. The unstructured N-terminal histone tails of all histones, but also the C-terminal tails of H2A histones protrude out of the compact structure of the nucleosome core...
February 27, 2018: Cancers
Miriam G Jasiulionis
Epigenetics refers to the study of mechanisms controlling the chromatin structure, which has fundamental role in the regulation of gene expression and genome stability. Epigenetic marks, such as DNA methylation and histone modifications, are established during embryonic development and epigenetic profiles are stably inherited during mitosis, ensuring cell differentiation and fate. Under the effect of intrinsic and extrinsic factors, such as metabolic profile, hormones, nutrition, drugs, smoke, and stress, epigenetic marks are actively modulated...
2018: Frontiers in Immunology
Yuanxin Xi, Jiejun Shi, Wenqian Li, Kaori Tanaka, Kendra L Allton, Dana Richardson, Jing Li, Hector L Franco, Anusha Nagari, Venkat S Malladi, Luis Della Coletta, Melissa S Simper, Khandan Keyomarsi, Jianjun Shen, Mark T Bedford, Xiaobing Shi, Michelle C Barton, W Lee Kraus, Wei Li, Sharon Y R Dent
BACKGROUND: Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy. RESULTS: To define alterations in epigenetic landscapes in breast cancers, we profiled the distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO-seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines that represent 5 molecular subtypes of breast cancer and immortalized human mammary epithelial cells...
February 20, 2018: BMC Genomics
Arundhati Bag, Niladri Bag
Tea polyphenols are secondary metabolites of tea plants and are well known for beneficial health effects. They can protect from a variety of illnesses including cancers. Tea polyphenols can prevent cancer by modulating epigenetic aberrations taking place in DNA methylation, histone modifications, and micro-RNAs. By altering these epimutations, they regulate chromatin dynamics and expression of genes those induce or suppress cancer formation. However, majority of the studies in existing literature are carried out for green tea polyphenols rather than black tea polyphenols despite the fact that black tea is the most commonly consumed form of tea (78%) followed by green tea (20%) and other forms of tea...
January 2018: Journal of Natural Science, Biology, and Medicine
Stefan J Tekel, Daniel A Vargas, Lusheng Song, Joshua LaBear, Michael R Caplan, Karmella A Haynes
Fusion proteins that specifically interact with biochemical marks on chromosomes represent a new class of synthetic transcriptional regulators that decode cell state information rather than DNA sequences. In multicellular organisms, information relevant to cell state, tissue identity, and oncogenesis is often encoded as biochemical modifications of histones, which are bound to DNA in eukaryotic nuclei and regulate gene expression states. We have previously reported the development and validation of the "Polycomb-based transcription factor" (PcTF), a fusion protein that recognizes histone modifications through a protein-protein interaction between its polycomb chromodomain (PCD) motif and trimethylated lysine 27 of histone H3 (H3K27me3) at genomic sites...
February 12, 2018: ACS Synthetic Biology
Chunwan Lu, Dafeng Yang, Maria E Sabbatini, Aaron H Colby, Mark W Grinstaff, Nicholas H Oberlies, Cedric Pearce, Kebin Liu
BACKGROUND: Pancreas ductal adenocarcinoma (PDAC) has the most dismal prognosis among all human cancers since it is highly resistant to chemotherapy, radiotherapy and immunotherapy. The anticipated consequence of all therapies is induction of tumor apoptosis. The highly resistance nature of PDACs to all therapies suggests that the intrinsic tumor cell factors, likely the deregulated apoptosis pathway, are key mechanisms underlying PDAC non-response to these therapies, rather than the therapeutic agents themselves...
February 6, 2018: BMC Cancer
Fade Gong, Kyle M Miller
Our genetic information is organized into chromatin, which consists of histones and proteins involved in regulating DNA compaction, accessibility and function. Chromatin is decorated by histone modifications, which provide signals that coordinate DNA-based processes including transcription and DNA damage response (DDR) pathways. A major signal involved in these processes is acetylation, which when attached to lysines within proteins, including histones, can be recognized and read by bromodomain-containing proteins...
February 2, 2018: Cell Cycle
Amanda N Henning, Rahul Roychoudhuri, Nicholas P Restifo
Upon stimulation, small numbers of naive CD8+ T cells proliferate and differentiate into a variety of memory and effector cell types. CD8+ T cells can persist for years and kill tumour cells and virally infected cells. The functional and phenotypic changes that occur during CD8+ T cell differentiation are well characterized, but the epigenetic states that underlie these changes are incompletely understood. Here, we review the epigenetic processes that direct CD8+ T cell differentiation and function. We focus on epigenetic modification of DNA and associated histones at genes and their regulatory elements...
January 30, 2018: Nature Reviews. Immunology
Yufeng Qin, John D Roberts, Sara A Grimm, Fred B Lih, Leesa J Deterding, Ruifang Li, Kaliopi Chrysovergis, Paul A Wade
BACKGROUND: The gut microbiome, a key constituent of the colonic environment, has been implicated as an important modulator of human health. The eukaryotic epigenome is postulated to respond to environmental stimuli through alterations in chromatin features and, ultimately, gene expression. How the host mediates epigenomic responses to gut microbiota is an emerging area of interest. Here, we profile the gut microbiome and chromatin characteristics in colon epithelium from mice fed either an obesogenic or control diet, followed by an analysis of the resultant changes in gene expression...
January 23, 2018: Genome Biology
Edward Curry, Constanze Zeller, Nahal Masrour, Darren Patten, John Gallon, Charlotte S Wilhelm-Benartzi, Sadaf Ghaem-Maghami, David D L Bowtell, Robert Brown
Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells aberrantly poised genes may facilitate changes in transcriptional states after exposure to anti-cancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3 and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue...
January 16, 2018: Cancer Research
Adam Cribbs, Edward S Hookway, Graham Wells, Morten Lindow, Susanna Obad, Henrik Oerum, Rab K Prinjha, Nick Athanasou, Aneka Sowman, Martin Philpott, Henry Penn, Kalle Soderstrom, Marc Feldmann, Udo Oppermann
Natural killer (NK) cells are innate lymphocytes, important in immune surveillance and elimination of stressed, transformed, or virus-infected cells. They critically shape the inflammatory cytokine environment to orchestrate interactions of cells of the innate and adaptive immune systems. Some studies have reported that NK cell activation and cytokine secretion are controlled epigenetically, but have yielded only limited insight into the mechanisms. Using chemical screening with small-molecule inhibitors of chromatin methylation and acetylation, further validated by knockdown approaches, we here identified Jumonji-type histone H3K27 demethylases as key regulators of cytokine production in human NK cell subsets...
January 4, 2018: Journal of Biological Chemistry
Prakriti Sen, Pooja Ganguly, Niladri Ganguly
Human papillomaviruses (HPVs) are double stranded circular DNA viruses that infect cutaneous and mucosal epithelial cells. Almost 99% of cervical cancer has a HPV infection. The early oncoproteins E6 and E7 are important in this cellular transformation process. Epigenetic mechanisms have long been known to result in decisive alterations in DNA, leading to alterations in DNA-protein interactions, alterations in chromatin structure and compaction and significant alterations in gene expression. The enzymes responsible for these epigenetic modifications are DNA methyl transferases (DNMTs), histone acetylases and deacetylases...
January 2018: Oncology Letters
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