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  • 1
    Publication Date: 2009-10-16
    Description: DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNA-protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes. Nearly one-quarter of all methylation identified in embryonic stem cells was in a non-CG context, suggesting that embryonic stem cells may use different methylation mechanisms to affect gene regulation. Methylation in non-CG contexts showed enrichment in gene bodies and depletion in protein binding sites and enhancers. Non-CG methylation disappeared upon induced differentiation of the embryonic stem cells, and was restored in induced pluripotent stem cells. We identified hundreds of differentially methylated regions proximal to genes involved in pluripotency and differentiation, and widespread reduced methylation levels in fibroblasts associated with lower transcriptional activity. These reference epigenomes provide a foundation for future studies exploring this key epigenetic modification in human disease and development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857523/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857523/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lister, Ryan -- Pelizzola, Mattia -- Dowen, Robert H -- Hawkins, R David -- Hon, Gary -- Tonti-Filippini, Julian -- Nery, Joseph R -- Lee, Leonard -- Ye, Zhen -- Ngo, Que-Minh -- Edsall, Lee -- Antosiewicz-Bourget, Jessica -- Stewart, Ron -- Ruotti, Victor -- Millar, A Harvey -- Thomson, James A -- Ren, Bing -- Ecker, Joseph R -- R01 HG003523/HG/NHGRI NIH HHS/ -- R01 HG003523-01/HG/NHGRI NIH HHS/ -- R01 HG003523-02/HG/NHGRI NIH HHS/ -- R01 HG003523-03/HG/NHGRI NIH HHS/ -- U01 1U01ES017166-01/ES/NIEHS NIH HHS/ -- U01 ES017166/ES/NIEHS NIH HHS/ -- England -- Nature. 2009 Nov 19;462(7271):315-22. doi: 10.1038/nature08514. Epub 2009 Oct 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829295" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Cluster Analysis ; DNA/metabolism ; *DNA Methylation ; DNA-Binding Proteins/metabolism ; Embryonic Stem Cells/metabolism ; *Epigenesis, Genetic ; Genome/*genetics ; Humans
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-02-20
    Description: Higher-order chromatin structure is emerging as an important regulator of gene expression. Although dynamic chromatin structures have been identified in the genome, the full scope of chromatin dynamics during mammalian development and lineage specification remains to be determined. By mapping genome-wide chromatin interactions in human embryonic stem (ES) cells and four human ES-cell-derived lineages, we uncover extensive chromatin reorganization during lineage specification. We observe that although self-associating chromatin domains are stable during differentiation, chromatin interactions both within and between domains change in a striking manner, altering 36% of active and inactive chromosomal compartments throughout the genome. By integrating chromatin interaction maps with haplotype-resolved epigenome and transcriptome data sets, we find widespread allelic bias in gene expression correlated with allele-biased chromatin states of linked promoters and distal enhancers. Our results therefore provide a global view of chromatin dynamics and a resource for studying long-range control of gene expression in distinct human cell lineages.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515363/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515363/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dixon, Jesse R -- Jung, Inkyung -- Selvaraj, Siddarth -- Shen, Yin -- Antosiewicz-Bourget, Jessica E -- Lee, Ah Young -- Ye, Zhen -- Kim, Audrey -- Rajagopal, Nisha -- Xie, Wei -- Diao, Yarui -- Liang, Jing -- Zhao, Huimin -- Lobanenkov, Victor V -- Ecker, Joseph R -- Thomson, James A -- Ren, Bing -- R01 ES024984/ES/NIEHS NIH HHS/ -- T32 GM007198/GM/NIGMS NIH HHS/ -- U01 ES017166/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Feb 19;518(7539):331-6. doi: 10.1038/nature14222.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA [2] Medical Scientist Training Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA. ; 1] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA [2] Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; The Morgridge Institute for Research, 309 North Orchard Street, Madison, Wisconsin 53715, USA. ; Tsinghua University-Peking University Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. ; Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. ; Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Twinbrook I NIAID Facility, Room 1417, 5640 Fishers Lane, Rockville, Maryland 20852, USA. ; Howard Hughes Medical Institute, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. ; 1] The Morgridge Institute for Research, 309 North Orchard Street, Madison, Wisconsin 53715, USA [2] Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA [3] Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara, California 93106, USA. ; 1] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653, USA [2] University of California, San Diego School of Medicine, Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25693564" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Allelic Imbalance/genetics ; *Cell Differentiation/genetics ; Cell Lineage/genetics ; Chromatin/*chemistry/genetics/*metabolism ; *Chromatin Assembly and Disassembly/genetics ; Embryonic Stem Cells/*cytology/*metabolism ; Enhancer Elements, Genetic/genetics ; Epigenesis, Genetic/*genetics ; Epigenomics ; Gene Regulatory Networks ; Humans ; Promoter Regions, Genetic/genetics ; Reproducibility of Results
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-07-06
    Description: DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785061/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785061/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lister, Ryan -- Mukamel, Eran A -- Nery, Joseph R -- Urich, Mark -- Puddifoot, Clare A -- Johnson, Nicholas D -- Lucero, Jacinta -- Huang, Yun -- Dwork, Andrew J -- Schultz, Matthew D -- Yu, Miao -- Tonti-Filippini, Julian -- Heyn, Holger -- Hu, Shijun -- Wu, Joseph C -- Rao, Anjana -- Esteller, Manel -- He, Chuan -- Haghighi, Fatemeh G -- Sejnowski, Terrence J -- Behrens, M Margarita -- Ecker, Joseph R -- AI44432/AI/NIAID NIH HHS/ -- CA151535/CA/NCI NIH HHS/ -- HD065812/HD/NICHD NIH HHS/ -- HG006827/HG/NHGRI NIH HHS/ -- K99NS080911/NS/NINDS NIH HHS/ -- MH094670/MH/NIMH NIH HHS/ -- R01 AI044432/AI/NIAID NIH HHS/ -- R01 CA151535/CA/NCI NIH HHS/ -- R01 HD065812/HD/NICHD NIH HHS/ -- R01 HG006827/HG/NHGRI NIH HHS/ -- R01 MH094670/MH/NIMH NIH HHS/ -- R01 MH094774/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Aug 9;341(6146):1237905. doi: 10.1126/science.1237905. Epub 2013 Jul 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. ryan.lister@uwa.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23828890" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/metabolism ; Adult ; Animals ; Base Sequence ; Conserved Sequence ; Cytosine/*analogs & derivatives/metabolism ; *DNA Methylation ; *Epigenesis, Genetic ; Epigenomics ; Frontal Lobe/*growth & development ; *Gene Expression Regulation, Developmental ; Genome-Wide Association Study ; Humans ; Longevity ; Mice ; Mice, Inbred C57BL ; X Chromosome Inactivation/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-07-11
    Description: Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the 'gold standard', they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ma, Hong -- Morey, Robert -- O'Neil, Ryan C -- He, Yupeng -- Daughtry, Brittany -- Schultz, Matthew D -- Hariharan, Manoj -- Nery, Joseph R -- Castanon, Rosa -- Sabatini, Karen -- Thiagarajan, Rathi D -- Tachibana, Masahito -- Kang, Eunju -- Tippner-Hedges, Rebecca -- Ahmed, Riffat -- Gutierrez, Nuria Marti -- Van Dyken, Crystal -- Polat, Alim -- Sugawara, Atsushi -- Sparman, Michelle -- Gokhale, Sumita -- Amato, Paula -- Wolf, Don P -- Ecker, Joseph R -- Laurent, Louise C -- Mitalipov, Shoukhrat -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jul 10;511(7508):177-83. doi: 10.1038/nature13551. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3]. ; 1] Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA [2]. ; 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Bioinformatics Program, University of California at San Diego, La Jolla, California 92093, USA. ; 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA. ; Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA. ; 1] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [2] Department of Obstetrics and Gynecology, South Miyagi Medical Center, Shibata-gun, Miyagi 989-1253, Japan (M.T.); Department of Cell and Molecular Biology, Karolinska Institutet, SE-17177 Stockholm, Sweden (A.P.). ; Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA. ; University Pathologists LLC, Boston University School of Medicine, Roger Williams Medical Center, Providence, Rhode Island 02118, USA. ; Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA. ; 1] Genomic Analysis Laboratory, the Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] Howard Hughes Medical Institute, the Salk Institute for Biological Studies, La Jolla, California 92037, USA. ; 1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3] Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25008523" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; *Cellular Reprogramming ; Chromosome Aberrations ; Chromosomes, Human, X/genetics/metabolism ; DNA Copy Number Variations ; DNA Methylation ; Genome-Wide Association Study ; Genomic Imprinting ; Humans ; Nuclear Transfer Techniques/standards ; Pluripotent Stem Cells/cytology/*metabolism ; Transcriptome
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2011-05-10
    Description: 5-hydroxymethylcytosine (5hmC) is a modified base present at low levels in diverse cell types in mammals. 5hmC is generated by the TET family of Fe(II) and 2-oxoglutarate-dependent enzymes through oxidation of 5-methylcytosine (5mC). 5hmC and TET proteins have been implicated in stem cell biology and cancer, but information on the genome-wide distribution of 5hmC is limited. Here we describe two novel and specific approaches to profile the genomic localization of 5hmC. The first approach, termed GLIB (glucosylation, periodate oxidation, biotinylation) uses a combination of enzymatic and chemical steps to isolate DNA fragments containing as few as a single 5hmC. The second approach involves conversion of 5hmC to cytosine 5-methylenesulphonate (CMS) by treatment of genomic DNA with sodium bisulphite, followed by immunoprecipitation of CMS-containing DNA with a specific antiserum to CMS. High-throughput sequencing of 5hmC-containing DNA from mouse embryonic stem (ES) cells showed strong enrichment within exons and near transcriptional start sites. 5hmC was especially enriched at the start sites of genes whose promoters bear dual histone 3 lysine 27 trimethylation (H3K27me3) and histone 3 lysine 4 trimethylation (H3K4me3) marks. Our results indicate that 5hmC has a probable role in transcriptional regulation, and suggest a model in which 5hmC contributes to the 'poised' chromatin signature found at developmentally-regulated genes in ES cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124347/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124347/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pastor, William A -- Pape, Utz J -- Huang, Yun -- Henderson, Hope R -- Lister, Ryan -- Ko, Myunggon -- McLoughlin, Erin M -- Brudno, Yevgeny -- Mahapatra, Sahasransu -- Kapranov, Philipp -- Tahiliani, Mamta -- Daley, George Q -- Liu, X Shirley -- Ecker, Joseph R -- Milos, Patrice M -- Agarwal, Suneet -- Rao, Anjana -- 1 R01 HD065812-01A1/HD/NICHD NIH HHS/ -- 1 UL1 RR 025758-02/RR/NCRR NIH HHS/ -- K08 HL089150/HL/NHLBI NIH HHS/ -- K08 HL089150-01A1/HL/NHLBI NIH HHS/ -- R01 AI044432/AI/NIAID NIH HHS/ -- R01 AI044432-10/AI/NIAID NIH HHS/ -- R01 AI44432/AI/NIAID NIH HHS/ -- R01 HD065812/HD/NICHD NIH HHS/ -- R01 HD065812-01A1/HD/NICHD NIH HHS/ -- RC1 DA028422/DA/NIDA NIH HHS/ -- RC1 DA028422-02/DA/NIDA NIH HHS/ -- UL1 RR025758/RR/NCRR NIH HHS/ -- England -- Nature. 2011 May 19;473(7347):394-7. doi: 10.1038/nature10102. Epub 2011 May 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard Medical School, Immune Disease Institute and Program in Cellular and Molecular Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21552279" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biotinylation ; Cell Line ; Cytosine/*analogs & derivatives/analysis/isolation & purification/metabolism ; DNA Methylation ; Embryonic Stem Cells/*metabolism ; Exons/genetics ; Gene Expression Regulation, Developmental/genetics ; Genome/*genetics ; Glucose/metabolism ; Mice ; Periodic Acid/metabolism ; Promoter Regions, Genetic/genetics ; Sequence Analysis, DNA/*methods ; Transcription Initiation Site ; Transcription, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
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  • 6
    Publication Date: 2011-02-04
    Description: Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem (ES) cells. However, it remains unknown how complete the reestablishment of ES-cell-like DNA methylation patterns is throughout the genome. Here we report the first whole-genome profiles of DNA methylation at single-base resolution in five human iPSC lines, along with methylomes of ES cells, somatic cells, and differentiated iPSCs and ES cells. iPSCs show significant reprogramming variability, including somatic memory and aberrant reprogramming of DNA methylation. iPSCs share megabase-scale differentially methylated regions proximal to centromeres and telomeres that display incomplete reprogramming of non-CG methylation, and differences in CG methylation and histone modifications. Lastly, differentiation of iPSCs into trophoblast cells revealed that errors in reprogramming CG methylation are transmitted at a high frequency, providing an iPSC reprogramming signature that is maintained after differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100360/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100360/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lister, Ryan -- Pelizzola, Mattia -- Kida, Yasuyuki S -- Hawkins, R David -- Nery, Joseph R -- Hon, Gary -- Antosiewicz-Bourget, Jessica -- O'Malley, Ronan -- Castanon, Rosa -- Klugman, Sarit -- Downes, Michael -- Yu, Ruth -- Stewart, Ron -- Ren, Bing -- Thomson, James A -- Evans, Ronald M -- Ecker, Joseph R -- 1U01ES017166-01/ES/NIEHS NIH HHS/ -- DK062434/DK/NIDDK NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- U01 ES017166/ES/NIEHS NIH HHS/ -- U01 ES017166-01/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Mar 3;471(7336):68-73. doi: 10.1038/nature09798. Epub 2011 Feb 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21289626" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Differentiation/genetics ; Cell Line ; Cellular Reprogramming/*genetics ; CpG Islands/genetics ; DNA Methylation/*genetics ; Embryonic Stem Cells/cytology/metabolism ; Epigenomics ; Epistasis, Genetic/*genetics ; Fibroblasts/cytology/metabolism ; Genome, Human/*genetics ; Histones/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology/*metabolism ; Trophoblasts/cytology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2013-03-08
    Description: Natural epigenetic variation provides a source for the generation of phenotypic diversity, but to understand its contribution to such diversity, its interaction with genetic variation requires further investigation. Here we report population-wide DNA sequencing of genomes, transcriptomes and methylomes of wild Arabidopsis thaliana accessions. Single cytosine methylation polymorphisms are not linked to genotype. However, the rate of linkage disequilibrium decay amongst differentially methylated regions targeted by RNA-directed DNA methylation is similar to the rate for single nucleotide polymorphisms. Association analyses of these RNA-directed DNA methylation regions with genetic variants identified thousands of methylation quantitative trait loci, which revealed the population estimate of genetically dependent methylation variation. Analysis of invariably methylated transposons and genes across this population indicates that loci targeted by RNA-directed DNA methylation are epigenetically activated in pollen and seeds, which facilitates proper development of these structures.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798000/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmitz, Robert J -- Schultz, Matthew D -- Urich, Mark A -- Nery, Joseph R -- Pelizzola, Mattia -- Libiger, Ondrej -- Alix, Andrew -- McCosh, Richard B -- Chen, Huaming -- Schork, Nicholas J -- Ecker, Joseph R -- F32 HG004830/HG/NHGRI NIH HHS/ -- F32HG004830/HG/NHGRI NIH HHS/ -- K99 GM100000/GM/NIGMS NIH HHS/ -- K99GM100000/GM/NIGMS NIH HHS/ -- UL1 RR025774/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Mar 14;495(7440):193-8. doi: 10.1038/nature11968. Epub 2013 Mar 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23467092" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/*genetics ; DNA Methylation/genetics ; DNA Transposable Elements/genetics ; Epigenesis, Genetic/*genetics ; Epigenomics ; Genetic Variation/*genetics ; Genome, Plant/*genetics ; Linkage Disequilibrium/genetics ; Pollen/genetics ; Polymorphism, Genetic/genetics ; Quantitative Trait Loci ; RNA, Messenger/analysis/genetics ; RNA, Plant/genetics ; Seeds/genetics
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  • 8
    Publication Date: 2015-05-07
    Description: Pluripotency, the ability to generate any cell type of the body, is an evanescent attribute of embryonic cells. Transitory pluripotent cells can be captured at different time points during embryogenesis and maintained as embryonic stem cells or epiblast stem cells in culture. Since ontogenesis is a dynamic process in both space and time, it seems counterintuitive that these two temporal states represent the full spectrum of organismal pluripotency. Here we show that by modulating culture parameters, a stem-cell type with unique spatial characteristics and distinct molecular and functional features, designated as region-selective pluripotent stem cells (rsPSCs), can be efficiently obtained from mouse embryos and primate pluripotent stem cells, including humans. The ease of culturing and editing the genome of human rsPSCs offers advantages for regenerative medicine applications. The unique ability of human rsPSCs to generate post-implantation interspecies chimaeric embryos may facilitate our understanding of early human development and evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Jun -- Okamura, Daiji -- Li, Mo -- Suzuki, Keiichiro -- Luo, Chongyuan -- Ma, Li -- He, Yupeng -- Li, Zhongwei -- Benner, Chris -- Tamura, Isao -- Krause, Marie N -- Nery, Joseph R -- Du, Tingting -- Zhang, Zhuzhu -- Hishida, Tomoaki -- Takahashi, Yuta -- Aizawa, Emi -- Kim, Na Young -- Lajara, Jeronimo -- Guillen, Pedro -- Campistol, Josep M -- Esteban, Concepcion Rodriguez -- Ross, Pablo J -- Saghatelian, Alan -- Ren, Bing -- Ecker, Joseph R -- Izpisua Belmonte, Juan Carlos -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 May 21;521(7552):316-21. doi: 10.1038/nature14413. Epub 2015 May 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA. ; 1] Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA [2] The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA. ; The Salk Institute for Biological Studies, Genomic Analysis Laboratory, La Jolla, California 92037, USA. ; The Salk Institute for Biological Studies, Integrated Genomics, La Jolla, California 92037, USA. ; Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, Department of Cellular and Molecular Medicine, 9500 Gilman Drive, La Jolla, California 92093-0653, USA. ; 1] The Salk Institute for Biological Studies, Gene Expression Laboratory, La Jolla, California 92037, USA [2] Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan. ; Grado en Medicina, Universidad Catolica, San Antonio de Murcia, Campus de los Jeronimos, 135, Guadalupe 30107, Spain. ; 1] Grado en Medicina, Universidad Catolica, San Antonio de Murcia, Campus de los Jeronimos, 135, Guadalupe 30107, Spain [2] Fundacion Pedro Guillen, Clinica Cemtro, Avenida Ventisquero de la Condesa, 42, 28035 Madrid, Spain. ; Hospital Clinic of Barcelona, Carrer Villarroel, 170, 08036 Barcelona, Spain. ; University of California, Davis, Davis, California 95616, USA. ; The Salk Institute for Biological Studies, Peptide Biology Laboratory, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25945737" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Culture Techniques/methods ; Cell Line ; *Chimera ; Embryonic Stem Cells/cytology ; Female ; Germ Layers/cytology ; Humans ; Induced Pluripotent Stem Cells/cytology ; Male ; Mice ; Pan troglodytes ; Pluripotent Stem Cells/*cytology/metabolism ; Regenerative Medicine ; Species Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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