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https://www.readbyqxmd.com/read/29694837/planarian-flatworms-as-a-new-model-system-for-understanding-epigenetic-regulation-of-stem-cell-pluripotency-and-differentiation
#1
REVIEW
Anish Dattani, Divya Sridhar, Aziz Aboobaker
Planarian flatworms possess pluripotent stem cells (neoblasts) that are able to differentiate into all cell types that constitute the adult body plan. Consequently, planarians possess remarkable regenerative capabilities. Transcriptomic studies have revealed that gene expression is coordinated to maintain neoblast pluripotency, and ensure correct lineage specification during differentiation. But as yet they have not revealed how this regulation of expression is controlled. In this review, we propose that planarians represent a unique and effective system to study the epigenetic regulation of these processes in an in vivo context...
April 22, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29693124/regulation-of-the-expression-of-tumor-necrosis-factor%C3%A2-related-genes-by-abnormal-histone-h3k27-acetylation-implications-for-neural-tube-defects
#2
Chunlei Wan, Xiaozhen Liu, Baoling Bai, Haiyan Cao, Huili Li, Qin Zhang
The association between apoptosis and neural tube defects (NTDs) is recognized as important, however, the precise link remains to be elucidated. Epigenetic modifications in human NTDs have been detected previously. In the present study, the occurrence of epigenetic modifications in apoptosis‑related genes was investigated in a retinoic acid (RA)‑induced mouse NTD model. Among 84 key genes involved in programmed cell death, 13 genes, including tumor necrosis factor (Tnf), annexin A5, apoptosis inhibitor 5, Bcl2‑associated athanogene 3, baculoviral IAP repeat‑containing 3, caspase (Casp)12, Casp4, Casp8, lymphotoxin β receptor, NLR family, apoptosis inhibitory protein 2, TNF receptor superfamily (Tnfrsf)1a, TNF superfamily (Tnfs)f10 and Tnfsf12, were downregulated, whereas nucleolar protein 3 was upregulated in the RA‑induced NTD mice...
April 19, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29692417/non-canonical-functions-of-the-rb-protein-in-cancer
#3
REVIEW
Frederick A Dick, David W Goodrich, Julien Sage, Nicholas J Dyson
The canonical model of RB-mediated tumour suppression developed over the past 30 years is based on the regulation of E2F transcription factors to restrict cell cycle progression. Several additional functions have been proposed for RB, on the basis of which a non-canonical RB pathway can be described. Mechanistically, the non-canonical RB pathway promotes histone modification and regulates chromosome structure in a manner distinct from cell cycle regulation. These functions have implications for chemotherapy response and resistance to targeted anticancer agents...
April 24, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29692252/epigenetics-nutrition-disease-and-drug-development
#4
Kenneth Lundstrom
Epigenetic mechanisms comprising of DNA methylation, histone modifications and gene silencing by RNA interference have been strongly linked to the development and progression of various diseases. These findings have triggered research on epigenetic functions and signal pathways as targets for novel drug discovery. Dietary intake has also presented significant influence on human health and disease development and nutritional modifications have proven important in prevention, but also treatment of disease. Moreover, a strong link between nutrition and epigenetic changes has been established...
April 19, 2018: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29691401/methylated-dnmt1-and-e2f1-are-targeted-for-proteolysis-by-l3mbtl3-and-crl4-dcaf5-ubiquitin-ligase
#5
Feng Leng, Jiekai Yu, Chunxiao Zhang, Salvador Alejo, Nam Hoang, Hong Sun, Fei Lu, Hui Zhang
Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4DCAF5 ...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691366/mutual-inhibition-between-hdac9-and-mir-17-regulates-osteogenesis-of-human-periodontal-ligament-stem-cells-in-inflammatory-conditions
#6
Liya Li, Wenjia Liu, Hong Wang, Qianjuan Yang, Liqiang Zhang, Fang Jin, Yan Jin
Histone deacetylases (HDAC) plays important roles in the post-translational modifications of histone cores as well as non-histone targets. Many of them are involved in key inflammatory processes. Despite their importance, whether and how HDAC9 is regulated under inflammatory conditions remains unclear. The aim of this study was to evaluate the effects of HDAC9 under chronic inflammation condition in human periodontal ligament stromal cell (PDLSCs) and to explore the underlying regulatory mechanism. PDLSCs from healthy or periodontitis human tissue was compared...
April 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29691302/repressing-the-repressor-ezh2-mediates-macrophage-activation
#7
Annette E Neele, Menno P J de Winther
In this issue of JEM , Zhang et al. (https://doi.org/10.1084/jem.20171417) show that the suppressive epigenetic enzyme Ezh2 is an important regulator of macrophage activation. The absence of Ezh2 leads to reduced cytokine secretion and suppresses macrophage-dependent disease development. They identify the antiinflammatory factor Socs3 as an important target for Ezh2 and thus show that regulation of suppressive histone modifications controls macrophage activation in disease.
April 24, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29689276/withaferin-a-and-sulforaphane-regulate-breast-cancer-cell-cycle-progression-through-epigenetic-mechanisms
#8
Kendra J Royston, Bidisha Paul, Susan Nozell, Rajani Rajbhandari, Trygve O Tollefsbol
Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyltransferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction...
April 21, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29688601/de-novo-mutations-in-the-set-nuclear-proto-oncogene-encoding-a-component-of-the-inhibitor-of-histone-acetyltransferases-inhat-complex-in-patients-with-non-syndromic-intellectual-disability
#9
Servi Jc Stevens, Vyne van der Schoot, Magalie S Leduc, Tuula Rinne, Seema R Lalani, Marjan M Weiss, Johanna M van Hagen, Augusta Ma Lachmeijer, Sylvia G Stockler-Ipsiroglu, Anna Lehman, Han G Brunner
The role of disturbed chromatin remodelling in the pathogenesis of intellectual disability (ID) is well established and illustrated by de novo mutations found in a plethora of genes encoding for proteins of the epigenetic regulatory machinery. We describe mutations in the "SET nuclear proto-oncogene" (SET), encoding a component of the "inhibitor of acetyltransferases" (INHAT) complex, involved in transcriptional silencing. Using whole exome sequencing, four patients were identified with de novo mutations in the SET gene...
April 24, 2018: Human Mutation
https://www.readbyqxmd.com/read/29687888/epigenetics-of-aberrant-cardiac-wound-healing
#10
Adam Russell-Hallinan, Chris J Watson, John A Baugh
Remodeling of cardiac tissue architecture is essential for normal organ development and maintaining homeostasis after injury. Injurious insults to the heart, such as hypertension and myocardial infarction, promote cellular responses including stimulation of resident inflammatory cells, activation of endothelial cells and recruitment of immune cells, hypertrophy of cardiomyocytes, and activation of fibroblasts. The physiological goal of this coordinated cellular response is to repair damaged tissue while maintaining or restoring cardiac contractile function...
March 26, 2018: Comprehensive Physiology
https://www.readbyqxmd.com/read/29686779/valproic-acid-exposure-of-pregnant-rats-during-organogenesis-disturbs-pancreas-development-in-insulin-synthesis-and-secretion-of-the-offspring
#11
Komariah Komariah, Wasmen Manalu, Bambang Kiranadi, Adi Winarto, Ekowati Handharyani, M Orliando Roeslan
Valproic acid (VPA) plays a role in histone modifications that eventually inhibit the activity of histone deacetylase (HDAC), and will affect the expressions of genes Pdx1, Nkx6.1, and Ngn3 during pancreatic organogenesis. This experiment was designed to study the effect of VPA exposure in pregnant rats on the activity of HDAC that controls the expression of genes regulating the development of beta cells in the pancreas to synthesize and secrete insulin. This study used 30 pregnant Sprague-Dawley rats, divided into 4 groups, as follows: (1) a control group of pregnant rats without VPA administration, (2) pregnant rats administered with 250 mg VPA on day 10 of pregnancy, (3) pregnant rats administered with 250 mg VPA on day 13 of pregnancy, and (4) pregnant rats administered with 250 mg VPA on day 16 of pregnancy...
April 2018: Toxicological Research
https://www.readbyqxmd.com/read/29686419/dynamics-of-the-epigenetic-landscape-during-the-maternal-to-zygotic-transition
#12
REVIEW
Melanie A Eckersley-Maslin, Celia Alda-Catalinas, Wolf Reik
A remarkable epigenetic remodelling process occurs shortly after fertilization, which restores totipotency to the zygote. This involves global DNA demethylation, chromatin remodelling, genome spatial reorganization and substantial transcriptional changes. Key to these changes is the transition from the maternal environment of the oocyte to an embryonic-driven developmental expression programme, a process termed the maternal-to-zygotic transition (MZT). Zygotic genome activation occurs predominantly at the two-cell stage in mice and the eight-cell stage in humans, yet the dynamics of its control are still mostly obscure...
April 23, 2018: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29685973/epigenetic-drug-discovery-a-success-story-for-cofactor-interference
#13
REVIEW
A Ganesan
Within the past two decades, seven epigenetic drugs have received regulatory approval and numerous other candidates are currently in clinical trials. Among the epigenetic targets are the writer and eraser enzymes that are, respectively, responsible for the reversible introduction and removal of structural modifications in the nucleosome. This review discusses the progress achieved in the design and development of inhibitors against the key writer and eraser pairs: DNA methyltransferases and Tet demethylases; lysine/arginine methyltransferases and lysine demethylases; and histone acetyltransferases and histone deacetylases...
June 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29684212/cadmium-exposure-of-female-mice-impairs-the-meiotic-maturation-of-oocytes-and-subsequent-embryonic-development
#14
Jia-Qiao Zhu, Yang Liu, Jiang-Hong Zhang, Yan-Fang Liu, Jiang-Qin Cao, Zhu-Tao Huang, Yan Yuan, Jian-Chun Bian, Zong-Ping Liu
Cadmium is one major pollutant that is highly toxic to animals and humans. The mechanism of cadmium toxicity on the female reproductive system, particularly oocyte maturation and fertility, remains to be clarified. In the present study, we used a mouse model to investigate the effects of cadmium in the drinking water on the meiotic maturation of oocytes and subsequent embryonic development, and the underlying mechanisms associated with the impairment of oocyte maturation such as mitochondrial distribution and histone modifications...
April 19, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29683440/an-integrated-platform-for-genome-wide-mapping-of-chromatin-states-using-high-throughput-chip-sequencing-in-tumor-tissues
#15
Christopher Terranova, Ming Tang, Elias Orouji, Mayinuer Maitituoheti, Ayush Raman, Samirkumar Amin, Zhiyi Liu, Kunal Rai
Histone modifications constitute a major component of the epigenome and play important regulatory roles in determining the transcriptional status of associated loci. In addition, the presence of specific modifications has been used to determine the position and identity non-coding functional elements such as enhancers. In recent years, chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) has become a powerful tool in determining the genome-wide profiles of individual histone modifications...
April 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29682202/ctcf-kdm4a-complex-correlates-with-histone-modifications-that-negatively-regulate-chd5-gene-expression-in-cancer-cell-lines
#16
Lissania Guerra-Calderas, Rodrigo González-Barrios, Carlos César Patiño, Nicolás Alcaraz, Marisol Salgado-Albarrán, David Cantú de León, Clementina Castro Hernández, Yesennia Sánchez-Pérez, Héctor Aquiles Maldonado-Martínez, Inti A De la Rosa-Velazquez, Fernanda Vargas-Romero, Luis A Herrera, Alejandro García-Carrancá, Ernesto Soto-Reyes
Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. KDM4A is abnormally expressed in cancer, affecting the expression of multiple targets, such as the CHD5 gene. This enzyme localizes at the first intron of CHD5 , and the dissociation of KDM4A increases gene expression. In vitro assays showed that KDM4A-mediated demethylation is enhanced in the presence of CTCF, suggesting that CTCF could increase its enzymatic activity in vivo, however the specific mechanism by which CTCF and KDM4A might be involved in the CHD5 gene repression is poorly understood...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29680858/relationship-between-histone-deacetylase-3-hdac3-and-breast-cancer
#17
Zhuhong Cui, Mingjun Xie, Zhenru Wu, Yujun Shi
BACKGROUND The modification of histone acetylation and deacetylation is the most important mechanism of chromatin remodeling. These modifications are a subset of epigenetic alterations which affect tumorigenesis and progression through changes in gene expression and cell growth. Results of histone modification studies prompted us to explore the therapeutic and prognostic significance of histone deacetylase 3 (HDAC3) expression in patients with breast cancer. MATERIAL AND METHODS Immunohistochemical (IHC) staining was used to detect HDAC3 expression in a tissue microarray (TMA) that included 145 patients diagnosed with invasive ductal breast carcinoma...
April 22, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29679612/protein-arginine-methyltransferase-5-promotes-lung-cancer-metastasis-via-the-epigenetic-regulation-of-mir-99-family-fgfr3-signaling
#18
Pengyu Jing, Nan Zhao, Mingxiang Ye, Yong Zhang, Zhipei Zhang, Jianyong Sun, Zhengxin Wang, Jian Zhang, Zhongping Gu
Protein arginine methyltransferase 5 (PRMT5) functions as a tumor initiator to regulate several cancer progressions, such as proliferation and apoptosis, by catalyzing the symmetrical dimethylation (me2s) of arginine residues within targeted molecules. However, the exact role of PRMT5-mediated metastasis in lung cancer is not fully understood. Here, we illustrated its potential effects in lung cancer metastasis in vivo and vitro. PRMT5 was frequently overexpressed in lung tumors, and its expression was positively related to tumor stages, lymphatic metastasis and poor outcome...
April 18, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29679095/implication-of-the-vrk1-chromatin-kinase-in-the-signaling-responses-to-dna-damage-a-therapeutic-target
#19
REVIEW
Ignacio Campillo-Marcos, Pedro A Lazo
DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR)...
April 20, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29676588/lysine-acetyltransferase-inhibitors-structure-activity-relationships-and-potential-therapeutic-implications
#20
Francesco Fiorentino, Antonello Mai, Dante Rotili
Lysine acetylation is a post-translational modification of both histone and nonhistone proteins that is catalyzed by lysine acetyltransferases and plays a key role in numerous biological contexts. The dysregulation of this enzyme activity is implicated in many human pathologies such as cancer, neurological and inflammatory disorders. Many lysine acetyltransferase inhibitors (KATi) have been developed so far, but there is still the need for new, more potent, metabolically stable and selective KATi as chemical tools for studying KAT biology and/or as potential therapeutic agents...
April 20, 2018: Future Medicinal Chemistry
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