Articles

Global differences in specific histone H3 methylation are associated with overweight and type 2 diabetes

Epidemiological evidence indicates yet unknown epigenetic mechanisms underlying a propensity for overweight and type 2 diabetes. We analyzed the extent of methylation at lysine 4 and lysine 9 of histone H3 in ...

Authors: Åsa Jufvas, Simon Sjödin, Kim Lundqvist, Risul Amin, Alexander V Vener and Peter Strålfors

Epigenetic therapies: novel strategies for improving outcomes in myeloid malignancies

Authors: Charles Craddock

Histone deacetylase (HDAC) 1 and 2 are essential for normal T cell development and genomic stability in mice

Authors: Oliver M Dovey, George Vasilliou, Allan Bradley and Shaun M Cowley

Genomic analysis reveals epigenetic ‘addiction’ underpinning follicular lymphoma and its transformation – a rationale for targeted epigenetic therapies

Authors: Jessica Okosun, Csaba Bödör, Jun Wang, Shamzah Araf, Claude Chelala and Jude Fitzgibbon

Disruption of DNA methylation via S-adenosylhomocysteine is a key process in high incidence liver carcinogenesis

Authors: Leda Mirbahai, Tim D Williams, Guangliang Yin, Andrew D Southam, Ulf Sommer, Ning Li, John P Bignell, Brett P Lyons, Mark R Viant and James K Chipman

Comparative analysis of breast and colorectal tumours uncouples loss of DNA methylation in cancer from association with the nuclear periphery

Authors: Elizabeth Kerr, Richard R Meehan, Wendy A Bickmore and Duncan Sproul

Understanding estrogen receptor transcription in breast cancer

Authors: Jason S Carroll

The role of BET epigenetic readers in acute myeloid leukaemia and other haematological malignancies

Authors: Brian Huntly

Cooperativity of imprinted genes inactivated by acquired chromosome 20q deletions

Authors: Athar Aziz, E Joanna Baxter, Carol Edwards, Clara Yujing Cheong, Mitsuteru Ito, Anthony Bench, Rebecca Kelley, Yvonne Silber, Philip A Beer, Keefe Chng, Marilyn B Renfree, Kirsten McEwen, Dionne Gray, Jyoti Nangalia, Ghulam J Mufti, Eva Hellstrom-Lindberg…

Regulation of proliferation and survival of B-lymphocytes by Ebf1 - implications in leukaemia

Authors: Ildikó Győry and Rudolf Grosschedl

Epigenetic modulation of distal regulatory elements in oral squamous cell carcinoma (OSCC)

Authors: Malgorzata Wiench, Songjoon Baek and Gordon Hager

FGF signalling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency

Authors: Gabriella Ficz, Timothy A Hore, Fatima Santos, Heather J Lee, Wendy Dean, Julia Arand, Felix Krueger, David Oxley, Yu-Lee Paul, Jörn Walter, Simon J Cook, Simon Andrews, Miguel R Branco and Wolf Reik

The dinucleotide CG as a genomic signalling module

Authors: Adrian Bird

Reduced expression of brain cannabinoid receptor 1 (Cnr1) is coupled with an increased complementary micro-RNA (miR-26b) in a mouse model of fetal alcohol spectrum disorders

Prenatal alcohol exposure is known to result in fetal alcohol spectrum disorders, a continuum of physiological, behavioural, and cognitive phenotypes that include increased risk for anxiety and learning-associ...

Authors: Randa L Stringer, Benjamin I Laufer, Morgan L Kleiber and Shiva M Singh

The combination of valproic acid, all-trans retinoic acid and low-dose cytarabine as disease-stabilizing treatment in acute myeloid leukemia

A large proportion of patients with acute myeloid leukemia (AML) are not fit for intensive and potentially curative therapy due to advanced age or comorbidity. Previous studies have demonstrated that a subset ...

Authors: Hanne Fredly, Elisabeth Ersvær, Astrid Olsnes Kittang, Galina Tsykunova, Bjørn Tore Gjertsen and Øystein Bruserud

Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents

Several new therapeutic strategies are now considered for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy, including modulation of protein lysine acetylation through inhibition of histon...

Authors: Hanne Fredly, Bjørn Tore Gjertsen and Øystein Bruserud

Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1

The NAD-dependent protein deacetylase SIRT1 has a wide range of different targets, which may be regulated either directly through deacetylation and thus potentially altering their activity or localization or i...

Authors: Judith Katto, Nicole Engel, Wasim Abbas, Georges Herbein and Ulrich Mahlknecht

Resveratrol, a sirtuin 1 activator, increases IL-6 production by peripheral blood mononuclear cells of patients with knee osteoarthritis

Sirtuin 1 (Sirt1) is a nuclear enzyme from the class III histone deacetylases that modulates gene expression and is involved in bone and cartilage remodeling. The goal of our study was to evaluate Sirt1 activi...

Authors: Daniel Wendling, Wasim Abbas, Marie Godfrin-Valnet, Xavier Guillot, Kashif Aziz Khan, Jean-Pierre Cedoz, Lucile Baud, Clément Prati and Georges Herbein

Specific inhibition of one DNMT1-including complex influences tumor initiation and progression

Reactivation of silenced tumor suppressor genes by DNMT inhibitors has provided an alternative approach to cancer therapy. However, DNMT inhibitors have also been shown to induce or enhance tumorigenesis via D...

Authors: Mathilde Cheray, Romain Pacaud, Arulraj Nadaradjane, François M Vallette and Pierre-François Cartron

Tissue-specific DNA methylation profiles in newborns

Epidemiological studies demonstrate that foetal growth restriction and low birth weight affect long-term health. Derangements in tissue-specific epigenetic programming of foetal and placental tissues are a sug...

Authors: Emilie Herzog, Jubby Galvez, Anton Roks, Lisette Stolk, Michael Verbiest, Paul Eilers, Jan Cornelissen, Eric Steegers and Régine Steegers-Theunissen

DNMT1 genetic polymorphisms affect breast cancer risk in the central European Caucasian population

DNA methylation of CpG islands within the promoter region of genes is an epigenetic modification with an important role in the development of cancer and it is typically mediated by DNA methyltransferases (DNMT...

Authors: Kathrin Kullmann, Mustafa Deryal, Mei Fang Ong, Werner Schmidt and Ulrich Mahlknecht

Differential placental methylation and expression of VEGF, FLT- 1 and KDR genes in human term and preterm preeclampsia

Preeclampsia, a pregnancy complication of placental origin is associated with altered expression of angiogenic factors and their receptors. Recently, there is considerable interest in understanding the role of...

Authors: Deepali P Sundrani, Umakar S Reddy, Asmita A Joshi, Savita S Mehendale, Preeti M Chavan-Gautam, Anandwardhan A Hardikar, Giriraj R Chandak and Sadhana R Joshi

Variation in ultraviolet radiation and diabetes: evidence of an epigenetic effect that modulates diabetics’ lifespan

Published research has shown that month-of-birth variations modulate the incidence of adult human diseases. This article explores diabetes type 2 as one of those diseases. This study uses the death records of ...

Authors: George E Davis and Walter E Lowell

Reviewer acknowledgement 2013

The editors of Clinical Epigenetics would like to thank all our reviewers who have contributed to the journal in volume 4 (2012).

Authors: Ulrich Mahlknecht

Pharmacokinetic and pharmacodynamic analysis of 5-aza-2’-deoxycytidine (decitabine) in the design of its dose-schedule for cancer therapy

5-Aza-2′-deoxycytidine (5-AZA-CdR, decitabine), an epigenetic drug that inhibits DNA methylation, is currently used to treat myelodysplastic syndrome (MDS), and is under investigation for treating acute myeloi...

Authors: Metin Karahoca and Richard L Momparler

BRAF mutation-specific promoter methylation of FOX genes in colorectal cancer

Cancer-specific hypermethylation of (promoter) CpG islands is common during the tumorigenesis of colon cancer. Although associations between certain genetic aberrations, such as BRAF mutation and microsatellite i...

Authors: Eddy H van Roon, Arnoud Boot, Ashwin A Dihal, Robert F Ernst, Tom van Wezel, Hans Morreau and Judith M Boer

The interaction of genetic variants and DNA methylation of the interleukin-4 receptor gene increase the risk of asthma at age 18 years

The occurrence of asthma is weakly explained by known genetic variants. Epigenetic marks, DNA methylation (DNA-M) in particular, are considered to add to the explanation of asthma. However, no etiological mode...

Authors: Nelís Soto-Ramírez, Syed Hasan Arshad, John W Holloway, Hongmei Zhang, Eric Schauberger, Susan Ewart, Veeresh Patil and Wilfried Karmaus

Evidence for transcript-specific epigenetic regulation of glucocorticoid-stimulated skeletal muscle 11β-hydroxysteroid dehydrogenase-1 activity in type 2 diabetes

The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) converts inactive cortisone into active cortisol in insulin target tissues. In people with type 2 diabetes, skeletal muscle (SkM) 11βHSD1 is upregul...

Authors: Warrick J Inder, Varuni R Obeyesekere, Christina Jang and Richard Saffery

Putative molecular mechanism underlying sperm chromatin remodelling is regulated by reproductive hormones

The putative regulatory role of the male reproductive hormones in the molecular mechanism underlying chromatin condensation remains poorly understood. In the past decade, we developed two adult male rat models...

Authors: Manjeet Kaur Gill-Sharma, Jyoti Choudhuri, Mukhtar Aleem Ansari and Serena D’Souza

A systematic evaluation of whole genome amplification of bisulfite-modified DNA

Studying DNA methylation profiles in detail should be the first step in epigenetic research. Although sodium bisulfite modification of genomic DNA is the gold standard method for DNA methylation analysis, this...

Authors: Miki Bundo, Fumiko Sunaga, Junko Ueda, Kiyoto Kasai, Tadafumi Kato and Kazuya Iwamoto

DNA methylation of the IGF2/H19 imprinting control region and adiposity distribution in young adults

The insulin-like growth factor 2 (IGF2) and H19 imprinted genes control growth and body composition. Adverse in-utero environments have been associated with obesity-related diseases and linked with altered DNA me...

Authors: Rae-Chi Huang, John C Galati, Sally Burrows, Lawrence J Beilin, Xin Li, Craig E Pennell, JAM van Eekelen, Trevor A Mori, Leon A Adams and Jeffrey M Craig

Genome-scale case-control analysis of CD4+ T-cell DNA methylation in juvenile idiopathic arthritis reveals potential targets involved in disease

Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune rheumatic disease of largely unknown cause. Evidence is growing that epigenetic variation, particularly DNA methylation, is associated with autoimmun...

Authors: Justine A Ellis, Jane E Munro, Raul A Chavez, Lavinia Gordon, Jihoon E Joo, Jonathan D Akikusa, Roger C Allen, Anne-Louise Ponsonby, Jeffrey M Craig and Richard Saffery

Vitamin and antioxidant rich diet increases MLH1 promoter DNA methylation in DMT2 subjects

Oxidative stress may lead to an increased level of unrepaired cellular DNA damage, which is discussed as one risk for tumor initiation. Mismatch repair (MMR) enzymes act as proofreading complexes that maintain...

Authors: Olivier J Switzeny, Elisabeth Müllner, Karl-Heinz Wagner, Helmut Brath, Eva Aumüller and Alexander G Haslberger

Sirtuin1 single nucleotide polymorphism (A2191G) is a diagnostic marker for vibration-induced white finger disease

Vibration-induced white finger disease (VWF), also known as hand-arm vibration syndrome, is a secondary form of Raynaud’s disease, affecting the blood vessels and nerves. So far, little is known about the path...

Authors: Susanne Voelter-Mahlknecht, Bernd Rossbach, Christina Schleithoff, Christian L Dransfeld, Stephan Letzel and Ulrich Mahlknecht

Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children

Secondhand smoke (SHS) and ambient air pollution (AAP) exposures have been associated with increased prevalence and severity of asthma and DNA modifications of immune cells. In the current study, we examined t...

Authors: Arunima Kohli, Marco A Garcia, Rachel L Miller, Christina Maher, Olivier Humblet, S Katharine Hammond and Kari Nadeau

A role for low-abundance miRNAs in colon cancer: the miR-206/Krüppel-like factor 4 (KLF4) axis

MicroRNAs (miRNAs or miRs) are short non-coding RNAs that affect the expression of genes involved in normal physiology, but that also become dysregulated in cancer development. In the latter context, studies t...

Authors: Mansi A Parasramka, W Mohaiza Dashwood, Rong Wang, Hassaan H Saeed, David E Williams, Emily Ho and Roderick H Dashwood

IGF2/H19 hypomethylation is tissue, cell, and CpG site dependent and not correlated with body asymmetry in adolescents with Silver-Russell syndrome

Silver-Russell syndrome (SRS) is characterized by severe intrauterine and postnatal growth failure and frequent body asymmetry. Half of the patients with SRS carry a DNA hypomethylation of the imprinting cente...

Authors: Kai Kannenberg, Karin Weber, Cathrin Binder, Christina Urban, Hans-Joachim Kirschner and Gerhard Binder

Milk kinship hypothesis in light of epigenetic knowledge

A wet nurse can be used if a baby’s natural mother is unable or chooses not to breastfeed her infant. The practice of using wet nurses is ancient and common to many cultures.

Authors: Hasan Ozkan, Funda Tuzun, Abdullah Kumral and Nuray Duman

Epigenetic alterations in preneoplastic and neoplastic lesions of the cervix

Cervical cancer (CC) is one of the most malignant tumors and the second or third most common type of cancer in women worldwide. The association between human papillomavirus (HPV) and CC is widely known and acc...

Authors: Kathleen P Saavedra, Priscilla M Brebi and Juan Carlos S Roa

Epigenetic dysregulation of secreted frizzled-related proteins in myeloproliferative neoplasms complements the JAK2V617F-mutation

Secreted frizzled-related proteins (SFRPs) are antagonists of the Wnt signaling pathway, which plays a central role in stem cell maintenance and differentiation of stem cells and hematopoietic progenitors. Epigen...

Authors: Karla Bennemann, Oliver Galm, Stefan Wilop, Claudia Schubert, Tim H Brümmendorf and Edgar Jost

DNA promoter methylation as a diagnostic and therapeutic biomarker in gallbladder cancer

Gallbladder cancer is an infrequent neoplasia with noticeable geographical variations in its incidence around the world. In Chile, it is the main cause of death owing to cancer in women over 40 years old, with...

Authors: Pablo Letelier, Priscilla Brebi, Oscar Tapia and Juan Carlos Roa

LINE-1 methylation in visceral adipose tissue of severely obese individuals is associated with metabolic syndrome status and related phenotypes

Epigenetic mechanisms may be involved in the regulation of genes found to be differentially expressed in the visceral adipose tissue (VAT) of severely obese subjects with (MetS+) versus without (MetS-) metabol...

Authors: Valérie Turcot, André Tchernof, Yves Deshaies, Louis Pérusse, Alexandre Bélisle, Simon Marceau, Simon Biron, Odette Lescelleur, Laurent Biertho and Marie-Claude Vohl

Hypermethylation of the 5′ CpG island of the p14^ARF flanking exon 1β in human colorectal cancer displaying a restricted pattern of p53 overexpression concomitant with increased MDM2 expression

It has been suggested that inactivation of p14^ARF, a tumor suppressor central to regulating p53 protein stability through interaction with the MDM2 oncoprotein, abrogates p53 activity in human tumors retaining th...

Authors: Christine Nyiraneza, Christine Sempoux, Roger Detry, Alex Kartheuser and Karin Dahan

Delivery type not associated with global methylation at birth

Birth by cesarean delivery (CD) as opposed to vaginal delivery (VD) is associated with altered health outcomes later in life, including respiratory disorders, allergies and risk of developing type I diabetes. ...

Authors: Shama Virani, Dana C Dolinoy, Sindhu Halubai, Tamara R Jones, Steve E Domino, Laura S Rozek, Muna S Nahar and Vasantha Padmanabhan

On the epigenetics of vascular regulation and disease

Consolidated knowledge is accumulating as to the role of epigenetic regulatory mechanisms in the physiology of vascular development and vascular tone as well as in the pathogenesis of cardiovascular disease. T...

Authors: Christina Schleithoff, Susanne Voelter-Mahlknecht, Indra Navina Dahmke and Ulrich Mahlknecht

A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States

The number of children ages 6 to 21 in the United States receiving special education services under the autism disability category increased 91% between 2005 to 2010 while the number of children receiving spec...

Authors: Renee Dufault, Walter J Lukiw, Raquel Crider, Roseanne Schnoll, David Wallinga and Richard Deth

Roles of histone deacetylases in epigenetic regulation: emerging paradigms from studies with inhibitors

The zinc-dependent mammalian histone deacetylase (HDAC) family comprises 11 enzymes, which have specific and critical functions in development and tissue homeostasis. Mounting evidence points to a link between...

Authors: Geneviève P Delcuve, Dilshad H Khan and James R Davie

The epigenetic effects of butyrate: potential therapeutic implications for clinical practice

Butyrate is a short chain fatty acid derived from the microbial fermentation of dietary fibers in the colon. In the last decade, multiple beneficial effects of butyrate at intestinal and extraintestinal level ...

Authors: Roberto Berni Canani, Margherita Di Costanzo and Ludovica Leone

Reproducibility and intraindividual variation over days in buccal cell DNA methylation of two asthma genes, interferon γ (IFNγ) and inducible nitric oxide synthase (iNOS)

The biological mechanisms responsible for the onset and exacerbation of asthma symptoms in children may involve the epigenetic regulation of inflammatory genes after environmental exposures. Using buccal cells...

Authors: DZ Torrone, JS Kuriakose, K Moors, H Jiang, MM Niedzwiecki, FF Perera and RL Miller

Is Friedreich ataxia an epigenetic disorder?

Friedreich ataxia (FRDA) is a debilitating and frequently fatal neurological disorder that is recessively inherited. It belongs to the group of genetic disorders known as the Repeat Expansion Diseases, in whic...

Authors: Daman Kumari and Karen Usdin