During my search for online resources, I found several useful websites on epigenetics research. I have written below the selected ones for easy access.
NOVA: Epigenetics
http://www.pbs.org/wgbh/nova/sciencenow/3411/02.html
NOVA: RNAi
http://www.pbs.org/wgbh/nova/sciencenow/3210/02.html
Science: Functional Epigenomics resources
http://www.sciencemag.org/feature/plus/sfg/resources/res_epigenetics.dtl
DNA Methylation Database
http://www.methdb.de/
Human Epigenome Project
http://www.epigenome.org/
Epigenetics Papers: Israel Barrantes’s Blog
http://epigenetica.blogspot.com/
The Epigenetics Center in the Institute for Basic Biomedical Sciences
Johns Hopkins School of Medicine
http://www.hopkinsmedicine.org/ibbs/research/epigenetics/
Centre for Epigenetics
http://www.epigenetics.dk/
Epigenetics Research
http://www.epidna.com/
Epigenetic and Methylation Station
http://www.epigeneticstation.com/
Epigenetics and Chromatin: Open Access Journal
http://www.epigeneticsandchromatin.com/
The Epigenome Network of Excellence
http://www.epigenome-noe.net/
The Epigenetics Database
http://www.epidna.com/database.php
Protocol Online
http://www.protocol-online.org/
The RNAi Web
http://www.rnaiweb.com/
Friday, August 1, 2008
Computational epigenetics.
Bioinformatics. 2008 Jan 1;24(1):1-10. Epub 2007 Nov 17.
Computational epigenetics.
Bock C, Lengauer T.
Max-Planck-Institut für Informatik, Saarbrücken, Germany. cbock@mpi-inf.mpg.de
Epigenetic research aims to understand heritable gene regulation that is not directly encoded in the DNA sequence. Epigenetic mechanisms such as DNA methylation and histone modifications modulate the packaging of the DNA in the nucleus and thereby influence gene expression. Patterns of epigenetic information are faithfully propagated over multiple cell divisions, which makes epigenetic regulation a key mechanism for cellular differentiation and cell fate decisions. In addition, incomplete erasure of epigenetic information can lead to complex patterns of non-Mendelian inheritance. Stochastic and environment-induced epigenetic defects are known to play a major role in cancer and ageing, and they may also contribute to mental disorders and autoimmune diseases. Recent technical advances such as ChIP-on-chip and ChIP-seq have started to convert epigenetic research into a high-throughput endeavor, to which bioinformatics is expected to make significant contributions. Here, we review pioneering computational studies that have contributed to epigenetic research. In addition, we give a brief introduction into epigenetics-targeted at bioinformaticians who are new to the field-and we outline future challenges in computational epigenetics.
PMID: 18024971 [PubMed - indexed for MEDLINE]
Link for Full Text: http://bioinformatics.oxfordjournals.org/cgi/content/full/24/1/1
Computational epigenetics.
Bock C, Lengauer T.
Max-Planck-Institut für Informatik, Saarbrücken, Germany. cbock@mpi-inf.mpg.de
Epigenetic research aims to understand heritable gene regulation that is not directly encoded in the DNA sequence. Epigenetic mechanisms such as DNA methylation and histone modifications modulate the packaging of the DNA in the nucleus and thereby influence gene expression. Patterns of epigenetic information are faithfully propagated over multiple cell divisions, which makes epigenetic regulation a key mechanism for cellular differentiation and cell fate decisions. In addition, incomplete erasure of epigenetic information can lead to complex patterns of non-Mendelian inheritance. Stochastic and environment-induced epigenetic defects are known to play a major role in cancer and ageing, and they may also contribute to mental disorders and autoimmune diseases. Recent technical advances such as ChIP-on-chip and ChIP-seq have started to convert epigenetic research into a high-throughput endeavor, to which bioinformatics is expected to make significant contributions. Here, we review pioneering computational studies that have contributed to epigenetic research. In addition, we give a brief introduction into epigenetics-targeted at bioinformaticians who are new to the field-and we outline future challenges in computational epigenetics.
PMID: 18024971 [PubMed - indexed for MEDLINE]
Link for Full Text: http://bioinformatics.oxfordjournals.org/cgi/content/full/24/1/1
Stability and flexibility of epigenetic gene regulation in mammalian development.
Nature. 2007 May 24;447(7143):425-32.
Stability and flexibility of epigenetic gene regulation in mammalian development.
Reik W.
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB22 3AT, UK. wolf.reik@bbsrc.ac.uk
During development, cells start in a pluripotent state, from which they can differentiate into many cell types, and progressively develop a narrower potential. Their gene-expression programmes become more defined, restricted and, potentially, 'locked in'. Pluripotent stem cells express genes that encode a set of core transcription factors, while genes that are required later in development are repressed by histone marks, which confer short-term, and therefore flexible, epigenetic silencing. By contrast, the methylation of DNA confers long-term epigenetic silencing of particular sequences--transposons, imprinted genes and pluripotency-associated genes--in somatic cells. Long-term silencing can be reprogrammed by demethylation of DNA, and this process might involve DNA repair. It is not known whether any of the epigenetic marks has a primary role in determining cell and lineage commitment during development.
PMID: 17522676 [PubMed - indexed for MEDLINE]
Link for Full Text: http://www.nature.com/nature/journal/v447/n7143/full/nature05918.html
Stability and flexibility of epigenetic gene regulation in mammalian development.
Reik W.
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB22 3AT, UK. wolf.reik@bbsrc.ac.uk
During development, cells start in a pluripotent state, from which they can differentiate into many cell types, and progressively develop a narrower potential. Their gene-expression programmes become more defined, restricted and, potentially, 'locked in'. Pluripotent stem cells express genes that encode a set of core transcription factors, while genes that are required later in development are repressed by histone marks, which confer short-term, and therefore flexible, epigenetic silencing. By contrast, the methylation of DNA confers long-term epigenetic silencing of particular sequences--transposons, imprinted genes and pluripotency-associated genes--in somatic cells. Long-term silencing can be reprogrammed by demethylation of DNA, and this process might involve DNA repair. It is not known whether any of the epigenetic marks has a primary role in determining cell and lineage commitment during development.
PMID: 17522676 [PubMed - indexed for MEDLINE]
Link for Full Text: http://www.nature.com/nature/journal/v447/n7143/full/nature05918.html
Epigenetic regulation of 11 beta-hydroxysteroid dehydrogenase type 2 expression.
J Clin Invest. 2004 Oct;114(8):1146-57.
Epigenetic regulation of 11 beta-hydroxysteroid dehydrogenase type 2 expression.
Alikhani-Koopaei R, Fouladkou F, Frey FJ, Frey BM.
Department of Nephrology and Hypertension, University Hospital of Berne, Berne UNK 3010, Switzerland.
The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) is selectively expressed in aldosterone target tissues, where it confers aldosterone selectivity for the mineralocorticoid receptor by inactivating 11 beta-hydroxyglucocorticoids. Variable activity of 11 beta HSD2 is relevant for blood pressure control and hypertension. The present investigation aimed to elucidate whether an epigenetic mechanism, DNA methylation, accounts for the rigorous control of expression of the gene encoding 11 beta HSD2, HSD11B2. CpG islands covering the promoter and exon 1 of HSD11B2 were found to be densely methylated in tissues and cell lines with low expression but not those with high expression of HSD11B2. Demethylation induced by 5-aza-2'-deoxycytidine and procainamide enhanced the transcription and activity of the 11 beta HSD2 enzyme in human cells in vitro and in rats in vivo. Methylation of HSD11B2 promoter-luciferase constructs decreased transcriptional activity. Methylation of recognition sequences of transcription factors, including those for Sp1/Sp3, Arnt, and nuclear factor 1 (NF1) diminished their DNA-binding activity. Herein NF1 was identified as a strong HSD11B2 stimulatory factor. The effect of NF1 was dependent on the position of CpGs and the combination of CpGs methylated. A methylated-CpG-binding protein complex 1 transcriptional repression interacted directly with the methylated HSD11B2 promoter. These results indicate a role for DNA methylation in HSD11B2 gene repression and suggest an epigenetic mechanism affecting this gene causally linked with hypertension.
PMID: 15489962 [PubMed - indexed for MEDLINE]
Link for Full Text: http://www.jci.org/articles/view/21647
Epigenetic regulation of 11 beta-hydroxysteroid dehydrogenase type 2 expression.
Alikhani-Koopaei R, Fouladkou F, Frey FJ, Frey BM.
Department of Nephrology and Hypertension, University Hospital of Berne, Berne UNK 3010, Switzerland.
The enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) is selectively expressed in aldosterone target tissues, where it confers aldosterone selectivity for the mineralocorticoid receptor by inactivating 11 beta-hydroxyglucocorticoids. Variable activity of 11 beta HSD2 is relevant for blood pressure control and hypertension. The present investigation aimed to elucidate whether an epigenetic mechanism, DNA methylation, accounts for the rigorous control of expression of the gene encoding 11 beta HSD2, HSD11B2. CpG islands covering the promoter and exon 1 of HSD11B2 were found to be densely methylated in tissues and cell lines with low expression but not those with high expression of HSD11B2. Demethylation induced by 5-aza-2'-deoxycytidine and procainamide enhanced the transcription and activity of the 11 beta HSD2 enzyme in human cells in vitro and in rats in vivo. Methylation of HSD11B2 promoter-luciferase constructs decreased transcriptional activity. Methylation of recognition sequences of transcription factors, including those for Sp1/Sp3, Arnt, and nuclear factor 1 (NF1) diminished their DNA-binding activity. Herein NF1 was identified as a strong HSD11B2 stimulatory factor. The effect of NF1 was dependent on the position of CpGs and the combination of CpGs methylated. A methylated-CpG-binding protein complex 1 transcriptional repression interacted directly with the methylated HSD11B2 promoter. These results indicate a role for DNA methylation in HSD11B2 gene repression and suggest an epigenetic mechanism affecting this gene causally linked with hypertension.
PMID: 15489962 [PubMed - indexed for MEDLINE]
Link for Full Text: http://www.jci.org/articles/view/21647
Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension.
Circ Res. 2007 Mar 2;100(4):520-6. Epub 2007 Jan 25.
Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension.
Bogdarina I, Welham S, King PJ, Burns SP, Clark AJ.
Centre for Endocrinology, Barts & the London, Queen Mary University of London, UK.
Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Lifelong environmental factors (eg, salt intake, obesity, alcohol) and genetic factors clearly contribute to the development of hypertension, but it has also been established that stress in utero may program the later development of the disease. This phenomenon, known as fetal programming can be modeled in a range of experimental animal models. In maternal low protein diet rat models of programming, administration of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists in early life can prevent development of hypertension, thus implicating the renin-angiotensin system in this process. Here we show that in this model, expression of the AT(1b) angiotensin receptor gene in the adrenal gland is upregulated by the first week of life resulting in increased receptor protein expression consistent with the increased adrenal angiotensin responsiveness observed by others. Furthermore, we show that the proximal promoter of the AT(1b) gene in the adrenal is significantly undermethylated, and that in vitro, AT(1b) gene expression is highly dependent on promoter methylation. These data suggest a link between fetal insults to epigenetic modification of genes and the resultant alteration of gene expression in adult life leading ultimately to the development of hypertension. It seems highly probable that similar influences may be involved in the development of human hypertension.
PMID: 17255528 [PubMed - indexed for MEDLINE]
Link for Full Text: http://circres.ahajournals.org/cgi/content/full/100/4/520
Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension.
Bogdarina I, Welham S, King PJ, Burns SP, Clark AJ.
Centre for Endocrinology, Barts & the London, Queen Mary University of London, UK.
Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Lifelong environmental factors (eg, salt intake, obesity, alcohol) and genetic factors clearly contribute to the development of hypertension, but it has also been established that stress in utero may program the later development of the disease. This phenomenon, known as fetal programming can be modeled in a range of experimental animal models. In maternal low protein diet rat models of programming, administration of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists in early life can prevent development of hypertension, thus implicating the renin-angiotensin system in this process. Here we show that in this model, expression of the AT(1b) angiotensin receptor gene in the adrenal gland is upregulated by the first week of life resulting in increased receptor protein expression consistent with the increased adrenal angiotensin responsiveness observed by others. Furthermore, we show that the proximal promoter of the AT(1b) gene in the adrenal is significantly undermethylated, and that in vitro, AT(1b) gene expression is highly dependent on promoter methylation. These data suggest a link between fetal insults to epigenetic modification of genes and the resultant alteration of gene expression in adult life leading ultimately to the development of hypertension. It seems highly probable that similar influences may be involved in the development of human hypertension.
PMID: 17255528 [PubMed - indexed for MEDLINE]
Link for Full Text: http://circres.ahajournals.org/cgi/content/full/100/4/520
Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.
Environ Health Perspect. 2006 Apr;114(4):567-72.
Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.
Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL.
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Genistein, the major phytoestrogen in soy, is linked to diminished female reproductive performance and to cancer chemoprevention and decreased adipose deposition. Dietary genistein may also play a role in the decreased incidence of cancer in Asians compared with Westerners, as well as increased cancer incidence in Asians immigrating to the United States. Here, we report that maternal dietary genistein supplementation of mice during gestation, at levels comparable with humans consuming high-soy diets, shifted the coat color of heterozygous viable yellow agouti (A(vy/a) offspring toward pseudoagouti. This marked phenotypic change was significantly associated with increased methylation of six cytosine-guanine sites in a retrotransposon upstream of the transcription start site of the Agouti gene. The extent of this DNA methylation was similar in endodermal, mesodermal, and ectodermal tissues, indicating that genistein acts during early embryonic development. Moreover, this genistein-induced hypermethylation persisted into adulthood, decreasing ectopic Agouti expression and protecting offspring from obesity. Thus, we provide the first evidence that in utero dietary genistein affects gene expression and alters susceptibility to obesity in adulthood by permanently altering the epigenome.
PMID: 16581547 [PubMed - indexed for MEDLINE]
Link for Full Text: http://www.ehponline.org/members/2006/8700/8700.html
Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.
Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL.
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Genistein, the major phytoestrogen in soy, is linked to diminished female reproductive performance and to cancer chemoprevention and decreased adipose deposition. Dietary genistein may also play a role in the decreased incidence of cancer in Asians compared with Westerners, as well as increased cancer incidence in Asians immigrating to the United States. Here, we report that maternal dietary genistein supplementation of mice during gestation, at levels comparable with humans consuming high-soy diets, shifted the coat color of heterozygous viable yellow agouti (A(vy/a) offspring toward pseudoagouti. This marked phenotypic change was significantly associated with increased methylation of six cytosine-guanine sites in a retrotransposon upstream of the transcription start site of the Agouti gene. The extent of this DNA methylation was similar in endodermal, mesodermal, and ectodermal tissues, indicating that genistein acts during early embryonic development. Moreover, this genistein-induced hypermethylation persisted into adulthood, decreasing ectopic Agouti expression and protecting offspring from obesity. Thus, we provide the first evidence that in utero dietary genistein affects gene expression and alters susceptibility to obesity in adulthood by permanently altering the epigenome.
PMID: 16581547 [PubMed - indexed for MEDLINE]
Link for Full Text: http://www.ehponline.org/members/2006/8700/8700.html
Epigenetic differences arise during the lifetime of monozygotic twins.
Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9. Epub 2005 Jul 11.
Epigenetic differences arise during the lifetime of monozygotic twins.
Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suñer D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M.
Epigenetics Laboratory, Spanish National Cancer Centre (CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain.
Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.
PMID: 16009939 [PubMed - indexed for MEDLINE]
Link for Full Text: http://www.pnas.org/content/102/30/10604.full
Epigenetic differences arise during the lifetime of monozygotic twins.
Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suñer D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M.
Epigenetics Laboratory, Spanish National Cancer Centre (CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain.
Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.
PMID: 16009939 [PubMed - indexed for MEDLINE]
Link for Full Text: http://www.pnas.org/content/102/30/10604.full
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