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  • September 28, 2016
  • 11:10 AM

When the writing is wrong: PRMT5 histone arginine methylation promotes invasivity and metastasis in a range of human cancers

by David Schecter in EpiBeat

Cancer metastasis occurs when cancer cells leave a primary tumor and invade other tissues. Generally, this leads to a poor prognosis for patients. Underlying epigenetic mechanisms of tumor progression are poorly understood but are of great interest for developing new approaches of treatment in the clinic. Cancer etiology is highly correlated with alterations in the histone code1-5 and protein methyltransferases are frequently dysregulated in cancer, implicating them as compelling novel targets f........ Read more »

Stopa N, Krebs JE, & Shechter D. (2015) The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond. Cellular and molecular life sciences : CMLS, 72(11), 2041-59. PMID: 25662273  

Sebova K, & Fridrichova I. (2010) Epigenetic tools in potential anticancer therapy. Anti-cancer drugs, 21(6), 565-77. PMID: 20436342  

Yang, Y., & Bedford, M. (2012) Protein arginine methyltransferases and cancer. Nature Reviews Cancer, 13(1), 37-50. DOI: 10.1038/nrc3409  

Greenblatt SM, Liu F, & Nimer SD. (2016) Arginine methyltransferases in normal and malignant hematopoiesis. Experimental hematology, 44(6), 435-41. PMID: 27026282  

Chan-Penebre E, Kuplast KG, Majer CR, Boriack-Sjodin PA, Wigle TJ, Johnston LD, Rioux N, Munchhof MJ, Jin L, Jacques SL.... (2015) A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models. Nature chemical biology, 11(6), 432-7. PMID: 25915199  

Liu F, Cheng G, Hamard PJ, Greenblatt S, Wang L, Man N, Perna F, Xu H, Tadi M, Luciani L.... (2015) Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis. The Journal of clinical investigation, 125(9), 3532-44. PMID: 26258414  

Ikushima H, & Miyazono K. (2010) TGFbeta signalling: a complex web in cancer progression. Nature reviews. Cancer, 10(6), 415-24. PMID: 20495575  

Lamouille, S., Xu, J., & Derynck, R. (2014) Molecular mechanisms of epithelial–mesenchymal transition. Nature Reviews Molecular Cell Biology, 15(3), 178-196. DOI: 10.1038/nrm3758  

  • September 14, 2016
  • 08:00 AM

5-Formlycytosine (5fC): A new base?

by Eliza Bacon in EpiBeat

DNA methylation and hydroxymethylation are well-established key players in gene regulation. Although many would agree that 5hmC also plays a critical role, there is still some debate over whether it serves a functional role, or is merely an artifact of DNA de-methylation. Even still, other intermediates of de-methylation are actively being investigated. In a recent paper by Iuilaro et al. 2016, a group of scientists argue that 5-formlycytosine (5fC), an intermediate of DNA de-methylation, is a s........ Read more »

Iurlaro M, McInroy GR, Burgess HE, Dean W, Raiber EA, Bachman M, Beraldi D, Balasubramanian S, & Reik W. (2016) In vivo genome-wide profiling reveals a tissue-specific role for 5-formylcytosine. Genome biology, 17(1), 141. PMID: 27356509  

  • August 24, 2016
  • 07:30 AM

Epigenetics of Early Pregnancy Loss: Hypomethylation and Genetic Instability May Contribute to Decreased Implantation Potential of Monosomy Blastocysts

by Blair McCallie in EpiBeat

Aneuploidy is the leading cause of miscarriage, stillbirth, and congenital birth defects and occurs as a result of errors during meiotic or mitotic cell division.1 As a woman ages, the probability of an aneuploid conception significantly rises, to roughly 50% by the age of 40.2 Only a fraction of full aneuploidies, primarily trisomies, will develop past the first trimester. This is in contrast to monosomies that almost never implant or result in an ongoing pregnancy. DNA methylation is an epi........ Read more »

  • July 27, 2016
  • 09:30 AM

HPV Human Papillomavirus Leads to Dysregulation of Immune Responses Through Epigenetic Mechanisms

by Louis Cicchini in EpiBeat

Human papillomaviruses (HPV) are a diverse group of small double-stranded DNA viruses with specific mucosal or cutaneous tropisms. It is estimated that up to 80% of sexually active individuals will become infected with HPV sometime in their lifetime, making HPV the most prevalent sexually transmitted infection. HPVs can be further divided into high- and low-risk genotypes, based on their oncogenic potential. High-risk HPVs are implicated as causal in nearly 100% of cervical cancers, approximatel........ Read more »

Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A.... (2011) The mutational landscape of head and neck squamous cell carcinoma. Science (New York, N.Y.), 333(6046), 1157-60. PMID: 21798893  

Burgers WA, Blanchon L, Pradhan S, de Launoit Y, Kouzarides T, & Fuks F. (2007) Viral oncoproteins target the DNA methyltransferases. Oncogene, 26(11), 1650-5. PMID: 16983344  

Schlecht NF, Kulaga S, Robitaille J, Ferreira S, Santos M, Miyamura RA, Duarte-Franco E, Rohan TE, Ferenczy A, Villa LL.... (2001) Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia. JAMA, 286(24), 3106-14. PMID: 11754676  

  • July 20, 2016
  • 08:30 AM

The “neighborhood effect” in chromatin biology: TET proteins-mediated DNA demethylation reconfigures the “histone code” at CpG islands

by Li Tan in EpiBeat

A nucleosome is constituted by positively charged histone proteins and negatively charged DNA. Methylation as well as other covalent modifications on DNA and histones ( together also called epigenetic modifications or marks) play important roles in the regulation of chromatin structure and function. TET (Ten-Eleven Translocation) proteins were identified as 5mC oxidases which not only generate new 5mC oxidative derivates (5hmC, 5caC and 5fC) but also initiate active or passive DNA demethylation1........ Read more »

Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L.... (2009) Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science (New York, N.Y.), 324(5929), 930-5. PMID: 19372391  

He YF, Li BZ, Li Z, Liu P, Wang Y, Tang Q, Ding J, Jia Y, Chen Z, Li L.... (2011) Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science (New York, N.Y.), 333(6047), 1303-7. PMID: 21817016  

Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, & Zhang Y. (2011) Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science (New York, N.Y.), 333(6047), 1300-3. PMID: 21778364  

Easwaran H, Johnstone SE, Van Neste L, Ohm J, Mosbruger T, Wang Q, Aryee MJ, Joyce P, Ahuja N, Weisenberger D.... (2012) A DNA hypermethylation module for the stem/progenitor cell signature of cancer. Genome research, 22(5), 837-49. PMID: 22391556  

Lian CG, Xu Y, Ceol C, Wu F, Larson A, Dresser K, Xu W, Tan L, Hu Y, Zhan Q.... (2012) Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma. Cell, 150(6), 1135-46. PMID: 22980977  

  • July 13, 2016
  • 07:30 AM

Plenty of Fish in the Sea but Only Two Kinds of Brains: Epigenetic Sex differences in Zebrafish Brain

by Aniruddha Chatterjee in EpiBeat

Phenotypic differences between males and females of a species are referred to as sexual dimorphism. Sexual dimorphism manifests not only in morphological traits, but also in physiological and behavioural traits. In organisms that do not have sex chromosomes, males and females are both derived from a nearly identical genome. Such is the case in zebrafish. Despite being such an important model for biological research, the mechanism of sex determination still remains a mystery. Many believe environ........ Read more »

Chatterjee A, Ozaki Y, Stockwell PA, Horsfield JA, Morison IM, & Nakagawa S. (2013) Mapping the zebrafish brain methylome using reduced representation bisulfite sequencing. Epigenetics, 8(9), 979-89. PMID: 23975027  

Chatterjee A, Stockwell PA, Horsfield JA, Morison IM, & Nakagawa S. (2014) Base-resolution DNA methylation landscape of zebrafish brain and liver. Genomics data, 342-4. PMID: 26484126  

Gagnidze K, Weil ZM, & Pfaff DW. (2010) Histone modifications proposed to regulate sexual differentiation of brain and behavior. BioEssays : news and reviews in molecular, cellular and developmental biology, 32(11), 932-9. PMID: 20836091  

  • July 6, 2016
  • 07:30 AM

Ancestral alcohol consumption may influence your drinking behavior and responses to stress

by Gregg E. Homanics in EpiBeat

Mice born to alcohol exposed fathers were resistant to stress-induced drinking. Read more on today's EpiBeat!... Read more »

  • October 29, 2014
  • 12:00 PM

Dopamine signaling leads to loss of polycomb repression and aberrant gene activation in experimental parkinsonism

by EpiBeat in EpiBeat

Parkinson’s disease (PD) is the second most frequent neurodegenerative disease, affecting 1-2% of the population over 55 years of age. The main pathological feature of PD is the progressive death of neurons located in the midbrain that produce the neurotransmitter dopamine.  These neurons modulate the activity of a collection of ...
The post Dopamine signaling leads to loss of polycomb repression and aberrant gene activation in experimental parkinsonism appeared first on EpiBeat.
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Birkmayer W, & Hornykiewicz O. (1998) The effect of l-3,4-dihydroxyphenylalanine (. Parkinsonism , 4(2), 59-60. PMID: 18591089  

Feyder M, Södersten E, Santini E, Vialou V, LaPlant Q, Watts EL, Spigolon G, Hansen K, Caboche J, Nestler EJ.... (2014) A Role for Mitogen- and Stress-Activated Kinase 1 in L-DOPA-Induced Dyskinesia and ∆FosB Expression. Biological psychiatry. PMID: 25193242  

Santini E, Valjent E, Usiello A, Carta M, Borgkvist A, Girault JA, Hervé D, Greengard P, & Fisone G. (2007) Critical involvement of cAMP/DARPP-32 and extracellular signal-regulated protein kinase signaling in L-DOPA-induced dyskinesia. The Journal of neuroscience : the official journal of the Society for Neuroscience, 27(26), 6995-7005. PMID: 17596448  

Di Croce, L., & Helin, K. (2013) Transcriptional regulation by Polycomb group proteins. Nature Structural , 20(10), 1147-1155. DOI: 10.1038/nsmb.2669  

  • October 22, 2014
  • 12:00 PM

Imprinting, epigenetic markers and assisted reproductive technologies (ARTs)

by EpiBeat in EpiBeat

Epigenetics refers to changes in gene regulation that are do not related to changes in the primary sequence of DNA. It can be reversible and heritable throughout cell division, and its regulation is characterized by several modifications, such as DNA methylation and post-translational changes in the histone proteins. In addition, ...
The post Imprinting, epigenetic markers and assisted reproductive technologies (ARTs) appeared first on EpiBeat.
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Carvalho JO, Michalczechen-Lacerda VA, Sartori R, Rodrigues FC, Bravim O, Franco MM, & Dode MA. (2012) The methylation patterns of the IGF2 and IGF2R genes in bovine spermatozoa are not affected by flow-cytometric sex sorting. Molecular reproduction and development, 79(2), 77-84. PMID: 22128039  

  • October 15, 2014
  • 11:00 AM

Artificial Transcription Factors – A new class of epigenetic drug

by EpiBeat in EpiBeat

Aberrant epigenetic status resulting in dysregulation of gene expression is a hallmark of many cancers and other diseases. In the last decade, countless time and energy has been spent in efforts to develop drugs targeting DNA methylation and histone modifications. To date however, none of these epigenetic drugs are sequence ...
The post Artificial Transcription Factors – A new class of epigenetic drug appeared first on EpiBeat.
... Read more »

  • October 9, 2014
  • 12:00 PM

Obesogens: The epigenetic interaction between nature and nurture on risk of obesity

by EpiBeat in EpiBeat

More than 35% of the U.S. population is considered clinically obese (body mass index of > 30), while 68% of the U.S. is considered overweight (body mass index of > 25) 1. Obesity is known to have adverse health effects, impacting the risk and prognosis for a number of diseases, ...
The post Obesogens: The epigenetic interaction between nature and nurture on risk of obesity appeared first on EpiBeat.
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McCormick DP, Sarpong K, Jordan L, Ray LA, & Jain S. (2010) Infant obesity: are we ready to make this diagnosis?. The Journal of pediatrics, 157(1), 15-9. PMID: 20338575  

Klimentidis, Y., Beasley, T., Lin, H., Murati, G., Glass, G., Guyton, M., Newton, W., Jorgensen, M., Heymsfield, S., Kemnitz, J.... (2010) Canaries in the coal mine: a cross-species analysis of the plurality of obesity epidemics. Proceedings of the Royal Society B: Biological Sciences, 278(1712), 1626-1632. DOI: 10.1098/rspb.2010.1890  

Grün F, & Blumberg B. (2009) Minireview: the case for obesogens. Molecular endocrinology (Baltimore, Md.), 23(8), 1127-34. PMID: 19372238  

Somm E, Schwitzgebel VM, Toulotte A, Cederroth CR, Combescure C, Nef S, Aubert ML, & Hüppi PS. (2009) Perinatal exposure to bisphenol a alters early adipogenesis in the rat. Environmental health perspectives, 117(10), 1549-55. PMID: 20019905  

Grün F, Watanabe H, Zamanian Z, Maeda L, Arima K, Cubacha R, Gardiner DM, Kanno J, Iguchi T, & Blumberg B. (2006) Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Molecular endocrinology (Baltimore, Md.), 20(9), 2141-55. PMID: 16613991  

Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies JL, Garratt E, Crozier SR.... (2011) Epigenetic gene promoter methylation at birth is associated with child's later adiposity. Diabetes, 60(5), 1528-34. PMID: 21471513  

  • June 20, 2014
  • 12:00 PM

Endothelial DNA Methylation Goes With the Flow

by EpiBeat in EpiBeat

Atherosclerosis is an inflammatory disease of the arterial walls, and is the major cause of heart attack and stroke. Atherosclerosis is localized to curves and branches in the vasculature where disturbed blood flow (d-flow) is able to alter gene expression and induce endothelial cell (EC) dysfunction. Our lab’s work focuses on the mechanism by which ...
The post Endothelial DNA Methylation Goes With the Flow appeared first on EpiBeat.
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  • June 13, 2014
  • 01:38 PM

SNP-SNP here, SNP-SNP there, everywhere a SNP-SNP, old McDonald had a GWAS……

by EpiBeat in EpiBeat

Gerhard A. Coetzee, Wange Lu, Peggy Farnham USC Genome-wide association studies (GWAS) have revealed numerous single-nucleotide polymorphisms (SNPs) where allelic frequencies differ between cases and controls of many complex diseases (NHGRI GWA Catalog). In the last decade 6,696 genetic associations of 598 traits have been reported in 16,770 papers (up to 2013). Despite these impressive ...
The post SNP-SNP here, SNP-SNP there, everywhere a SNP-SNP, old McDonald had a GWAS…… appeared first o........ Read more »

Hazelett DJ, Rhie SK, Gaddis M, Yan C, Lakeland DL, Coetzee SG, Ellipse/GAME-ON consortium, Practical consortium, Henderson BE, Noushmehr H.... (2014) Comprehensive functional annotation of 77 prostate cancer risk loci. PLoS genetics, 10(1). PMID: 24497837  

Eeles RA, Olama AA, Benlloch S, Saunders EJ, Leongamornlert DA, Tymrakiewicz M, Ghoussaini M, Luccarini C, Dennis J, Jugurnauth-Little S.... (2013) Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nature genetics, 45(4), 385. PMID: 23535732  

Visscher PM, Brown MA, McCarthy MI, & Yang J. (2012) Five years of GWAS discovery. American journal of human genetics, 90(1), 7-24. PMID: 22243964  

Ecker JR, Bickmore WA, Barroso I, Pritchard JK, Gilad Y, & Segal E. (2012) Genomics: ENCODE explained. Nature, 489(7414), 52-5. PMID: 22955614  

  • June 6, 2014
  • 12:35 PM

The Mitochondrial Epigenetic Revolution: A New Avenue for Potential Research

by EpiBeat in EpiBeat

The mitochondria, often referred to as the “power-house” of the cell, provide a platform for energy production through glucose metabolism. As a bi-product of this, they also are the major producer of reactive oxidative species. Mitochondria also play other important physiological roles, such as calcium homeostasis and aid in the regulation of cell death through ...
The post The Mitochondrial Epigenetic Revolution: A New Avenue for Potential Research appeared first on EpiBeat.
... Read more »

Chestnut BA, Chang Q, Price A, Lesuisse C, Wong M, & Martin LJ. (2011) Epigenetic regulation of motor neuron cell death through DNA methylation. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(46), 16619-36. PMID: 22090490  

Manev H, Dzitoyeva S, & Chen H. (2012) Mitochondrial DNA: A Blind Spot in Neuroepigenetics. Biomolecular concepts, 3(2), 107-115. PMID: 22639700  

Shock LS, Thakkar PV, Peterson EJ, Moran RG, & Taylor SM. (2011) DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. Proceedings of the National Academy of Sciences of the United States of America, 108(9), 3630-5. PMID: 21321201  

Wang C, & Youle RJ. (2009) The role of mitochondria in apoptosis*. Annual review of genetics, 95-118. PMID: 19659442  

  • May 16, 2014
  • 06:02 PM

The Battle for HOXC10 in the War Against Breast Cancer

by EpiBeat in EpiBeat

Tamoxifen and aromatase inhibitors (AIs) are both treatment options for patients with breast tumors that express estrogen receptor (ER) α and that require estrogen for growth. Tamoxifen competes with estrogen in binding to the ER, but does not activate the receptor. In comparison, AIs lower estrogen levels in the body by blocking the conversion of ...The post The Battle for HOXC10 in the War Against Breast Cancer appeared first on EpiBeat.... Read more »

Pathiraja TN, Nayak SR, Xi Y, Jiang S, Garee JP, Edwards DP, Lee AV, Chen J, Shea MJ, Santen RJ.... (2014) Epigenetic reprogramming of HOXC10 in endocrine-resistant breast cancer. Science translational medicine, 6(229). PMID: 24670685  

  • May 6, 2014
  • 12:00 PM

iPSC Epigenetic Memory: One more Roadblock for Regenerative Medicine?

by EpiBeat in EpiBeat

The discovery of induced pluripotent stem cells (iPSCs) and the creation of clinically relevant cell types derived from them, have been great leaps toward the implementation of stem cell based therapies and disease models. But in recent years, concerns have risen about iPSCs “remembering” their original cell types and favoring differentiation towards their origins.  This ...The post iPSC Epigenetic Memory: One more Roadblock for Regenerative Medicine? appeared first on EpiBeat.... Read more »

Roessler R, Smallwood SA, Veenvliet JV, Pechlivanoglou P, Peng SP, Chakrabarty K, Groot-Koerkamp MJ, Pasterkamp RJ, Wesseling E, Kelsey G.... (2014) Detailed Analysis of the Genetic and Epigenetic Signatures of iPSC-Derived Mesodiencephalic Dopaminergic Neurons. Stem cell reports, 2(4), 520-33. PMID: 24749075  

  • April 25, 2014
  • 06:24 PM

Maternal Diet Affects DNA Methylation Patterns in Offspring

by EpiBeat in EpiBeat

There is now mounting evidence that diet and other environmental factors can have widespread and long-lasting influences on a developing fetus. Historically, folic acid supplementation is recommended to pregnant mothers as a means to prevent developmental disorders and birth defects. However, there is still no clear understanding how such supplementation may influence a developing child’s ...The post Maternal Diet Affects DNA Methylation Patterns in Offspring appeared first on EpiBeat.... Read more »

  • April 7, 2014
  • 04:57 PM

April is Autism Awareness Month: Increased levels of 5-hmC may influence gene regulation in Autism Spectrum Disorder

by EpiBeat in EpiBeat

The prevalence of Autism Spectrum Disorder (ASD) has increased by roughly 30% since 2012. The CDC recently reported that one in 68 children in the United States is affected by ASD, compared to one in 88 just two years ago. This enhanced occurrence could be attributed to advancements in the detection and diagnosis, increased awareness, ...The post April is Autism Awareness Month: Increased levels of 5-hmC may influence gene regulation in Autism Spectrum Disorder appeared first on EpiBeat.... Read more »

  • March 31, 2014
  • 07:58 PM


by EpiBeat in EpiBeat

Breast cancer is one of the most common cancers worldwide in females. Researchers from the University of California, Los Angeles (UCLA) found that PIAS1 is linked to breast tumorigenesis. PIAS1 is a transcriptional repressor that has SUMO (small ubiquitin-like modifier) E3 ligase activity. Recently, it had been explored that PIAS1 facilitates a novel epigenetic mechanism ...The post NEW LINK FOUND BETWEEN BREAST CANCER AND EPIGENETICS appeared first on EpiBeat.... Read more »

Liu B, Tahk S, Yee KM, Yang R, Yang Y, Mackie R, Hsu C, Chernishof V, O'Brien N, Jin Y.... (2014) PIAS1 Regulates Breast Tumorigenesis through Selective Epigenetic Gene Silencing. PloS one, 9(2). PMID: 24586797  

  • March 19, 2014
  • 12:15 PM

Cigarette Smoking and Epigenetics: DNA Methylation Differences Between Ethnic Groups

by EpiBeat in EpiBeat

Cigarette smoking leads to some of the most preventable causes of death and illness in the world. The Centers for Disease Control (CDC) in the United States has reported that there are approximately 440,000 deaths due to smoking each year, and an additional 49,000 deaths due to secondhand smoke.  Roughly 600 chemicals are found in ...The post Cigarette Smoking and Epigenetics: DNA Methylation Differences Between Ethnic Groups appeared first on EpiBeat.... Read more »

Elliott HR, Tillin T, McArdle WL, Ho K, Duggirala A, Frayling TM, Davey Smith G, Hughes AD, Chaturvedi N, & Relton CL. (2014) Differences in smoking associated DNA methylation patterns in South Asians and Europeans. Clinical epigenetics, 6(1), 4. PMID: 24485148  

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