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https://www.readbyqxmd.com/read/28445939/epigenetic-therapy-with-inhibitors-of-histone-methylation-suppresses-dna-damage-signaling-and-increases-glioma-cell-radiosensitivity
#1
Ozge Gursoy-Yuzugullu, Chelsea Carman, Rodolfo Bortolozo Serafim, Marios Myronakis, Valeria Valente, Brendan D Price
Radiation therapy is widely used to treat human malignancies, but many tumor types, including gliomas, exhibit significant radioresistance. Radiation therapy creates DNA double-strand breaks (DSBs), and DSB repair is linked to rapid changes in epigenetic modifications, including increased histone methylation. This increased histone methylation recruits DNA repair proteins which can then alter the local chromatin structure and promote repair. Consequently, combining inhibitors of specific histone methyltransferases with radiation therapy may increase tumor radiosensitivity, particularly in tumors with significant therapeutic resistance...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445736/systematic-epigenomic-analysis-reveals-chromatin-states-associated-with-melanoma-progression
#2
Petko Fiziev, Kadir C Akdemir, John P Miller, Emily Z Keung, Neha S Samant, Sneha Sharma, Christopher A Natale, Christopher J Terranova, Mayinuer Maitituoheti, Samirkumar B Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B Axelrad, Amiksha Shah, Christine S Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C Barton, Alexei Protopopov, Kenneth Y Tsai, Michael A Davies, Benjamin A Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445605/high-throughput-cell-mechanical-phenotyping-for-label-free-titration-assays-of-cytoskeletal-modifications
#3
Stefan Golfier, Philipp Rosendahl, Alexander Mietke, Maik Herbig, Jochen Guck, Oliver Otto
The mechanical fingerprint of cells is inherently linked to the structure of the cytoskeleton and can serve as a label free marker for cell homeostasis or pathologic states. How cytoskeletal composition affects the physical response of cells to external loads has been intensively studied with a spectrum of techniques, yet quantitative and statistically powerful investigations in the form of titration assays are hampered by the low throughput of most available methods. In this study, we employ real-time deformability cytometry (RT-DC), a novel microfluidic tool to examine the effects of biochemically modified F-actin and microtubule stability and nuclear chromatin structure on cell deformation in a human leukemia cell line (HL60)...
April 26, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28445475/grhl3-binding-and-enhancers-rearrange-as-epidermal-keratinocytes-transition-between-functional-states
#4
Rachel Herndon Klein, Ziguang Lin, Amelia Soto Hopkin, William Gordon, Lam C Tsoi, Yun Liang, Johann E Gudjonsson, Bogi Andersen
Transcription factor binding, chromatin modifications and large scale chromatin re-organization underlie progressive, irreversible cell lineage commitments and differentiation. We know little, however, about chromatin changes as cells enter transient, reversible states such as migration. Here we demonstrate that when human progenitor keratinocytes either differentiate or migrate they form complements of typical enhancers and super-enhancers that are unique for each state. Unique super-enhancers for each cellular state link to gene expression that confers functions associated with the respective cell state...
April 26, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28445112/tracking-the-evolution-of-non-small-cell-lung-cancer
#5
Mariam Jamal-Hanjani, Gareth A Wilson, Nicholas McGranahan, Nicolai J Birkbak, Thomas B K Watkins, Selvaraju Veeriah, Seema Shafi, Diana H Johnson, Richard Mitter, Rachel Rosenthal, Max Salm, Stuart Horswell, Mickael Escudero, Nik Matthews, Andrew Rowan, Tim Chambers, David A Moore, Samra Turajlic, Hang Xu, Siow-Ming Lee, Martin D Forster, Tanya Ahmad, Crispin T Hiley, Christopher Abbosh, Mary Falzon, Elaine Borg, Teresa Marafioti, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Rajesh Shah, Leena Joseph, Anne M Quinn, Phil A Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Stefan Dentro, Philippe Taniere, Brendan O'Sullivan, Helen L Lowe, John A Hartley, Natasha Iles, Harriet Bell, Yenting Ngai, Jacqui A Shaw, Javier Herrero, Zoltan Szallasi, Roland F Schwarz, Aengus Stewart, Sergio A Quezada, John Le Quesne, Peter Van Loo, Caroline Dive, Allan Hackshaw, Charles Swanton
Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC. Methods In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy...
April 26, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28442058/nuclear-transfer-alters-placental-gene-expression-and-associated-histone-modifications-of-the-placental-specific-imprinted-gene-pleckstrin-homology-like-domain-family-a-member-2-phlda2-in-cattle
#6
Daniel R Arnold, Roberta C Gaspar, Carlos V da Rocha, Juliano R Sangalli, Tiago H C de Bem, Carolina A P Corrêa, João C T Penteado, Flavio V Meirelles, Flavia L Lopes
Abnormal placental development is frequent in nuclear transfer (NT) pregnancies and is likely to be associated with altered epigenetic reprogramming. In the present study, fetal and placental measurements were taken on Day 60 of gestation in cows with pregnancies produced by AI, IVF and NT. Placentas were collected and subjected to histological evaluation, the expression of genes important in trophoblast differentiation and expression of the placental imprinted gene pleckstrin homology-like domain, family A, member 2 (PHLDA2), as well as chromatin immunoprecipitation (ChIP) for histone marks within the promoter of PHLDA2...
March 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28441948/over-expressed-long-noncoding-rna-hoxa11-as-promotes-cell-cycle-progression-and-metastasis-in-gastric-cancer
#7
Zhili Liu, Zhenyao Chen, Ruihua Fan, Bin Jiang, Xin Chen, Qinnan Chen, Fengqi Nie, Kaihua Lu, Ming Sun
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as critical regulators in a variety of human cancers, including gastric cancer (GC). However, the function and mechanisms responsible for these molecules in GC are not fully understood. In our previous study, we found that GC associated lncRNA HOXA11-AS is significantly upregulated in GC tissues. Over-expressed HOXA11-AS promotes GC cells proliferation and invasion through scaffolding the chromatin modification factors PRC2, LSD1 and DNMT1...
April 26, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28441589/nutrient-stress-induced-chromatin-changes-in-plants
#8
REVIEW
David Secco, James Whelan, Hatem Rouached, Ryan Lister
The ability of plants to appropriately respond to the soil nutrient availability is of primary importance for their development and to complete their life cycle. Deciphering these multifaceted adaptive mechanisms remains a major challenge for scientists to date. Recent technological breakthroughs now enable to assess the dynamism and complexity of these processes at unprecedented resolution. In this review, we present some of the most recent findings on the involvement of histone modifications, histone variants and DNA methylation in response to nutrient stresses as well as discussing the potential roles these chromatin changes could serve as priming or as trans-generational stress memory mechanisms...
April 22, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28441353/matrix-metalloproteinase-gene-activation-resulting-from-disordred-epigenetic-mechanisms-in-rheumatoid-arthritis
#9
REVIEW
Yasuto Araki, Toshihide Mimura
Matrix metalloproteinases (MMPs) are implicated in the degradation of extracellular matrix (ECM). Rheumatoid arthritis (RA) synovial fibroblasts (SFs) produce matrix-degrading enzymes, including MMPs, which facilitate cartilage destruction in the affected joints in RA. Epigenetic mechanisms contribute to change in the chromatin state, resulting in an alteration of gene transcription. Recently, MMP gene activation has been shown to be caused in RASFs by the dysregulation of epigenetic changes, such as histone modifications, DNA methylation, and microRNA (miRNA) signaling...
April 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28441146/epigenetic-regulation-of-glucose-metabolism
#10
Sapna Sharma, Jennifer Kriebel, Harald Grallert
PURPOSE OF REVIEW: Glucose metabolism is a central process in mammalian energy homeostasis. Its deregulation is a key factor in development of metabolic disease like diabetes and cancer. In recent decades, our understanding of gene regulation at the signaling, chromatin and posttranscriptional levels has seen dramatic developments. RECENT FINDINGS: A number of epigenetic mechanisms that do not affect the genetic code can be assessed with new technologies. However, increasing complexity becomes a major challenge for translation into clinical application...
April 24, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28440894/chromatin-sumoylation-in-heat-stress-to-protect-pause-and-organise-sumo-stress-response-on-chromatin
#11
REVIEW
Einari A Niskanen, Jorma J Palvimo
Post-translational modifications, e.g. SUMO modifications (SUMOylation), provide a mechanism for swiftly changing a protein's activity. Various stress conditions trigger a SUMO stress response (SSR) - a stress-induced rapid change in the conjugation of SUMO to multiple proteins, which predominantly targets nuclear proteins. The SSR has been postulated to protect stressed cells by preserving the functionality of crucial proteins. However, it is unclear how it exerts its protective functions. Interestingly, heat stress (HS) increases SUMOylation of proteins at active promoters and enhancers...
April 25, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28439859/genome-wide-profiling-of-histone-modifications-and-histone-variants-in-arabidopsis-thaliana-and-marchantia-polymorpha
#12
Ramesh Yelagandula, Akihisa Osakabe, Elin Axelsson, Frederic Berger, Tomokazu Kawashima
Histone modifications and histone variants barcode the genome and play major roles in epigenetic regulations. Chromatin immunoprecipitation (ChIP) coupled with next-generation sequencing (NGS) is a well-established method to investigate the landscape of epigenetic marks at a genomic level. Here, we describe procedures for conducting ChIP, subsequent NGS library construction, and data analysis on histone modifications and histone variants in Arabidopsis thaliana. We also describe an optimized nuclear isolation procedure to prepare chromatin for ChIP in the liverwort, Marchantia polymorpha, which is the emerging model plant ideal for evolutionary studies...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28433423/prefrontal-cortex-expression-of-chromatin-modifier-genes-in-male-wsp-and-wsr-mice-changes-across-ethanol-dependence-withdrawal-and-abstinence
#13
Joel G Hashimoto, David P Gavin, Kristine M Wiren, John C Crabbe, Marina Guizzetti
Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines...
March 14, 2017: Alcohol
https://www.readbyqxmd.com/read/28433419/disconnect-between-alcohol-induced-alterations-in-chromatin-structure-and-gene-transcription-in-a-mouse-embryonic-stem-cell-model-of-exposure
#14
Kylee J Veazey, Haiqing Wang, Yudhishtar S Bedi, William M Skiles, Richard Cheng-An Chang, Michael C Golding
Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program...
January 11, 2017: Alcohol
https://www.readbyqxmd.com/read/28432837/identifying-genetic-sources-of-phenotypic-heterogeneity-in-orofacial-clefts-by-targeted-sequencing
#15
Jenna C Carlson, Margaret A Taub, Eleanor Feingold, Terri H Beaty, Jeffrey C Murray, Mary L Marazita, Elizabeth J Leslie
BACKGROUND: Orofacial clefts (OFCs), including nonsyndromic cleft lip with or without cleft palate (NSCL/P), are common birth defects. NSCL/P is highly heterogeneous with multiple phenotypic presentations. Two common subtypes of NSCL/P are cleft lip (CL) and cleft lip with cleft palate (CLP) which have different population prevalence. Similarly, NSCL/P can be divided into bilateral and unilateral clefts, with unilateral being the most common. Individuals with unilateral NSCL/P are more likely to be affected on the left side of the upper lip, but right side affection also occurs...
April 22, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28432332/involvement-of-gonadotropin-inhibitory-hormone-in-pubertal-disorders-induced-by-thyroid-status
#16
Mika Kiyohara, You Lee Son, Kazuyoshi Tsutsui
Thyroid disorders cause abnormal puberty, indicating interactions between the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG) axes, which are important in pubertal development. The hypothalamic gonadotropin-inhibitory hormone (GnIH) was shown to be decreased in the early prepubertal stage, suggesting the role of GnIH on pubertal onset. Here, we investigated whether thyroid dysfunction affects pubertal onset in female mice via GnIH regulation. Hypothyroidism showed delayed pubertal onset with increased GnIH expression and reduced pituitary-gonadal activity...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432260/dual-histone-reader-zmynd8-inhibits-cancer-cell-invasion-by-positively-regulating-epithelial-genes
#17
Moitri Basu, Isha Sengupta, Wasim Khan, Dushyant Kumar Srivastava, Partha Chakrabarti, Siddhartha Roy, Chandrima Das
Enhanced migratory potential and invasiveness of cancer cells attribute crucially.in cancer progression. These phenotypes are achieved by precise alteration of invasion-associated genes through local epigenetic modifications which are recognized by a class of proteins termed as chromatin reader. ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a key component of transcription regulatory network, has been recently shown to be a novel reader of H3.1K36Me2/H4K16Ac marks. Through differential gene expression analysis upon silencing this chromatin reader, we identified a subset of genes involved in cell proliferation and invasion/migration regulated by ZMYND8...
April 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28429743/novel-sumo-protease-senp7s-regulates-%C3%AE-catenin-signaling-and-mammary-epithelial-cell-transformation
#18
Samaneh Karami, Feng-Ming Lin, Santosh Kumar, Shaymaa Bahnassy, Hariprasad Thangavel, Maram Quttina, Yue Li, Jing Ren, Tasneem Bawa-Khalfe
SUMO post-translational modification of proteins or SUMOylation ensures normal cell function. Disruption of SUMO dynamics prompts various pathophysiological conditions, including cancer. The burden of deSUMOylating the large SUMO-proteome rests on 6 full-length mammalian SUMO-proteases or SENP. While multiple SENP isoforms exist, the function of these isoforms remains undefined. We now delineate the biological role of a novel SENP7 isoform SENP7S in mammary epithelial cells. SENP7S is the predominant SENP transcript in human mammary epithelia but is significantly reduced in precancerous ductal carcinoma in situ and all breast cancer subtypes...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429219/effects-of-different-modes-of-hypobaric-hypoxia-on-the-content-of-epigenetic-factors-in-the-rat-in-neurons-of-rat-neocortex
#19
M O Samoilov, A V Churilova, T S Glushchenko, E A Rybnikova
We studied the effects of different modes of hypobaric hypoxia on the content of epigenetic factors acH3K24, meH3K9, and meDNA modulating conformational characteristics of chromatin and gene expression in neurons of associative complex of rat parietal neocortex. Severe destructive hypoxia dramatically reduced the level of acH3K24 in 3 h after the end of exposure and increased meH3K9 and meDNA content. By contrast, 3-fold (but not single) adaptive exposure to moderate hypobaric hypoxia that produced a neuroprotective effect enhanced neuronal acH3K24 expression and decreased both meH3K9 and meDNA levels...
April 21, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428957/coordinating-regulation-of-gene-expression-in-cardiovascular-disease-interactions-between-chromatin-modifiers-and-transcription-factors
#20
REVIEW
Ashley J Bauer, Kathleen A Martin
Cardiovascular disease is a leading cause of death with increasing economic burden. The pathogenesis of cardiovascular diseases is complex, but can arise from genetic and/or environmental risk factors. This can lead to dysregulated gene expression in numerous cell types including cardiomyocytes, endothelial cells, vascular smooth muscle cells, and inflammatory cells. While initial studies addressed transcriptional control of gene expression, epigenetics has been increasingly appreciated to also play an important role in this process through alterations in chromatin structure and gene accessibility...
2017: Frontiers in Cardiovascular Medicine
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