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Article ; Online: Nucleosome Occupancy and Methylome Sequencing (NOMe-seq).

Lay, Fides D / Kelly, Theresa K / Jones, Peter A

Methods in molecular biology (Clifton, N.J.)

2017 Volume 1708, Page(s) 267–284

Abstract: Various methodologies are available to interrogate specific components of epigenetic mechanisms such as DNA methylation or nucleosome occupancy at both the locus-specific and the genome-wide level. It has become increasingly clear, however, that ... ...

Abstract	Various methodologies are available to interrogate specific components of epigenetic mechanisms such as DNA methylation or nucleosome occupancy at both the locus-specific and the genome-wide level. It has become increasingly clear, however, that comprehension of the functional interactions between epigenetic mechanisms is critical for understanding how cellular transcription programs are regulated or deregulated during normal and disease development. The Nucleosome Occupancy and Methylome sequencing (NOMe-seq) assay allows us to directly measure the relationship between DNA methylation and nucleosome occupancy by taking advantage of the methyltransferase M.CviPI, which methylates unprotected GpC dinucleotides to create a footprint of chromatin accessibility. This assay generates dual nucleosome occupancy and DNA methylation information at a single-DNA molecule resolution using as little as 200,000 cells and in as short as 15 min reaction time. DNA methylation levels and nucleosome occupancy status of genomic regions of interest can be subsequently interrogated by cloning PCR-amplified bisulfite DNA and sequencing individual clones. Alternatively, NOMe-seq can be combined with next-generation sequencing in order to generate an integrated global map of DNA methylation and nucleosome occupancy, which allows for comprehensive examination as to how these epigenetic components correlate with each other.
MeSH term(s)	CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Methyltransferases/metabolism ; Nucleosomes/metabolism ; Promoter Regions, Genetic ; Sequence Analysis, DNA/methods
Chemical Substances	Nucleosomes ; Methyltransferases (EC 2.1.1.-)
Language	English
Publishing date	2017-10-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7481-8_14
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Article ; Online: Monitoring plasma nucleosome concentrations to measure disease response and progression in dogs with hematopoietic malignancies.

Wilson-Robles, Heather / Warry, Emma / Miller, Tasha / Jarvis, Jill / Matsushita, Matthew / Miller, Pamela / Herzog, Marielle / Turatsinze, Jean-Valery / Kelly, Theresa K / Butera, S Thomas / Michel, Gaetan

PloS one

2023 Volume 18, Issue 5, Page(s) e0281796

Abstract: Background: Hematopoietic malignancies are extremely common in pet dogs and represent nearly 30% of the malignancies diagnosed in this population each year. Clinicians commonly use existing tools such as physical exam findings, radiographs, ultrasound ... ...

Abstract	Background: Hematopoietic malignancies are extremely common in pet dogs and represent nearly 30% of the malignancies diagnosed in this population each year. Clinicians commonly use existing tools such as physical exam findings, radiographs, ultrasound and baseline blood work to monitor these patients for treatment response and remission. Circulating biomarkers, such as prostate specific antigen or carcinoembryonic antigen, can be useful tools for monitoring treatment response and remission status in human cancer patients. To date, there has a been a lack of useful circulating biomarkers available to veterinary oncology patients. Methods: Circulating plasma nucleosome concentrations were evaluated at diagnosis, throughout treatment and during remission monitoring for 40 dogs with lymphoma, acute myelogenous leukemia and multiple myeloma. Additionally, C-reactive protein and thymidine kinase-1 levels were recorded. Results: Plasma nucleosome concentrations were significantly higher at diagnosis and progressive disease than they were when dogs were in remission. All but two dogs had plasma nucleosome concentrations that returned to the low range during treatment. These two dogs had the shortest progression free and overall survival times. Dogs with the highest plasma nucleosome concentrations had a significantly shorter first progression free survival than dogs with lower plasma nucleosome concentrations at diagnosis. Plasma nucleosome concentrations correlated better with disease response and progression than either thymidine kinase or C reactive protein. Conclusions: Plasma nucleosome concentrations can be a useful tool for treatment monitoring and disease progression in dogs with hematopoietic malignancies.
MeSH term(s)	Male ; Humans ; Dogs ; Animals ; Nucleosomes ; Thymidine Kinase ; Biomarkers ; Neoplasms ; Hematologic Neoplasms/veterinary ; C-Reactive Protein ; Dog Diseases/diagnosis
Chemical Substances	Nucleosomes ; Thymidine Kinase (EC 2.7.1.21) ; Biomarkers ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2023-05-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0281796
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Article ; Online: Epigenetic regulation of transcriptional plasticity associated with developmental song learning.

Kelly, Theresa K / Ahmadiantehrani, Somayeh / Blattler, Adam / London, Sarah E

Proceedings. Biological sciences

2018 Volume 285, Issue 1878

Abstract: Ethologists discovered over 100 years ago that some lifelong behavioural patterns were acquired exclusively during restricted developmental phases called critical periods (CPs). Developmental song learning in zebra finches is one of the most striking ... ...

Abstract	Ethologists discovered over 100 years ago that some lifelong behavioural patterns were acquired exclusively during restricted developmental phases called critical periods (CPs). Developmental song learning in zebra finches is one of the most striking examples of a CP for complex learned behaviour. After post-hatch day 65, whether or not a juvenile male can memorize the song of a 'tutor' depends on his experiences in the month prior. If he experienced a tutor, he can no longer learn, but if he has been isolated from hearing a tutor the learning period is extended. We aimed to identify how tutor experience alters the brain and controls the ability to learn. Epigenetic landscapes are modulated by experience and are able to regulate the transcription of sets of genes, thereby affecting cellular function. Thus, we hypothesized that tutor experiences determine the epigenetic landscape in the auditory forebrain, a region required for tutor song memorization. Using ChIPseq, RNAseq and molecular biology, we provide evidence that naturalistic experiences associated with the ability to learn can induce epigenetic changes, and propose transcriptional plasticity as a mediator of CP learning potential.
MeSH term(s)	Animals ; Epigenesis, Genetic/physiology ; Finches/genetics ; Finches/physiology ; Gene Expression Regulation, Developmental ; Learning ; Male ; Music ; Songbirds/genetics ; Songbirds/physiology ; Transcription, Genetic ; Vocalization, Animal
Language	English
Publishing date	2018-05-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209242-6
ISSN	1471-2954 ; 0080-4649 ; 0962-8452 ; 0950-1193
ISSN (online)	1471-2954
ISSN	0080-4649 ; 0962-8452 ; 0950-1193
DOI	10.1098/rspb.2018.0160
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Article ; Online: Role of nucleosomes in mitotic bookmarking.

Kelly, Theresa K / Jones, Peter A

Cell cycle (Georgetown, Tex.)

2011 Volume 10, Issue 3, Page(s) 370–371

MeSH term(s)	Chromatin Assembly and Disassembly ; Epigenesis, Genetic ; Gene Expression Regulation/physiology ; Gene Silencing ; Mitosis ; Models, Genetic ; Nucleosomes/physiology ; Transcription Initiation Site
Chemical Substances	Nucleosomes
Language	English
Publishing date	2011-02-01
Publishing country	United States
Document type	Editorial
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.4161/cc.10.3.14734
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Article ; Online: Epigenetics in cancer.

Sharma, Shikhar / Kelly, Theresa K / Jones, Peter A

Carcinogenesis

2009 Volume 31, Issue 1, Page(s) 27–36

Abstract: Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Global changes ... ...

Abstract	Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Global changes in the epigenetic landscape are a hallmark of cancer. The initiation and progression of cancer, traditionally seen as a genetic disease, is now realized to involve epigenetic abnormalities along with genetic alterations. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer including DNA methylation, histone modifications, nucleosome positioning and non-coding RNAs, specifically microRNA expression. The reversible nature of epigenetic aberrations has led to the emergence of the promising field of epigenetic therapy, which is already making progress with the recent FDA approval of three epigenetic drugs for cancer treatment. In this review, we discuss the current understanding of alterations in the epigenetic landscape that occur in cancer compared with normal cells, the roles of these changes in cancer initiation and progression, including the cancer stem cell model, and the potential use of this knowledge in designing more effective treatment strategies.
MeSH term(s)	Epigenesis, Genetic ; Humans ; MicroRNAs/genetics ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplastic Stem Cells
Chemical Substances	MicroRNAs
Language	English
Publishing date	2009-09-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	603134-1
ISSN	1460-2180 ; 0143-3334
ISSN (online)	1460-2180
ISSN	0143-3334
DOI	10.1093/carcin/bgp220
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Article: Genome-wide nucleosome occupancy and DNA methylation profiling of four human cell lines.

Statham, Aaron L / Taberlay, Phillippa C / Kelly, Theresa K / Jones, Peter A / Clark, Susan J

Genomics data

2014 Volume 3, Page(s) 94–96

Abstract: DNA methylation and nucleosome positioning are two key mechanisms that contribute to the epigenetic control of gene expression. During carcinogenesis, the expression of many genes is altered alongside extensive changes in the epigenome, with repressed ... ...

Abstract	DNA methylation and nucleosome positioning are two key mechanisms that contribute to the epigenetic control of gene expression. During carcinogenesis, the expression of many genes is altered alongside extensive changes in the epigenome, with repressed genes often being associated with local DNA hypermethylation and gain of nucleosomes at their promoters. However the spectrum of alterations that occur at distal regulatory regions has not been extensively studied. To address this we used Nucleosome Occupancy and Methylation sequencing (NOMe-seq) to compare the genome-wide DNA methylation and nucleosome occupancy profiles between normal and cancer cell line models of the breast and prostate. Here we describe the bioinformatic pipeline and methods that we developed for the processing and analysis of the NOMe-seq data published by (Taberlay et al., 2014 [1]) and deposited in the Gene Expression Omnibus with accession GSE57498.
Language	English
Publishing date	2014-12-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2751131-5
ISSN	2213-5960
ISSN	2213-5960
DOI	10.1016/j.gdata.2014.11.012
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Article ; Online: Reconfiguration of nucleosome-depleted regions at distal regulatory elements accompanies DNA methylation of enhancers and insulators in cancer.

Taberlay, Phillippa C / Statham, Aaron L / Kelly, Theresa K / Clark, Susan J / Jones, Peter A

Genome research

2014 Volume 24, Issue 9, Page(s) 1421–1432

Abstract: It is well established that cancer-associated epigenetic repression occurs concomitant with CpG island hypermethylation and loss of nucleosomes at promoters, but the role of nucleosome occupancy and epigenetic reprogramming at distal regulatory elements ... ...

Abstract	It is well established that cancer-associated epigenetic repression occurs concomitant with CpG island hypermethylation and loss of nucleosomes at promoters, but the role of nucleosome occupancy and epigenetic reprogramming at distal regulatory elements in cancer is still poorly understood. Here, we evaluate the scope of global epigenetic alterations at enhancers and insulator elements in prostate and breast cancer cells using simultaneous genome-wide mapping of DNA methylation and nucleosome occupancy (NOMe-seq). We find that the genomic location of nucleosome-depleted regions (NDRs) is mostly cell type specific and preferentially found at enhancers in normal cells. In cancer cells, however, we observe a global reconfiguration of NDRs at distal regulatory elements coupled with a substantial reorganization of the cancer methylome. Aberrant acquisition of nucleosomes at enhancer-associated NDRs is associated with hypermethylation and epigenetic silencing marks, and conversely, loss of nucleosomes with demethylation and epigenetic activation. Remarkably, we show that nucleosomes remain strongly organized and phased at many facultative distal regulatory elements, even in the absence of a NDR as an anchor. Finally, we find that key transcription factor (TF) binding sites also show extensive peripheral nucleosome phasing, suggesting the potential for TFs to organize NDRs genome-wide and contribute to deregulation of cancer epigenomes. Together, our findings suggest that "decommissioning" of NDRs and TFs at distal regulatory elements in cancer cells is accompanied by DNA hypermethylation susceptibility of enhancers and insulator elements, which in turn may contribute to an altered genome-wide architecture and epigenetic deregulation in malignancy.
MeSH term(s)	DNA Methylation ; Enhancer Elements, Genetic ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Humans ; Insulator Elements ; MCF-7 Cells ; Nucleosomes/genetics ; Nucleosomes/metabolism
Chemical Substances	Nucleosomes
Language	English
Publishing date	2014-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.163485.113
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Zs.A 3729: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Genome-wide nucleosome occupancy and DNA methylation profiling of four human cell lines

Statham, Aaron L / Taberlay, Phillippa C / Kelly, Theresa K / Jones, Peter A / Clark, Susan J

Genomics Data. 2015 Mar., v. 3

2015

Abstract	DNA methylation and nucleosome positioning are two key mechanisms that contribute to the epigenetic control of gene expression. During carcinogenesis, the expression of many genes is altered alongside extensive changes in the epigenome, with repressed genes often being associated with local DNA hypermethylation and gain of nucleosomes at their promoters. However the spectrum of alterations that occur at distal regulatory regions has not been extensively studied. To address this we used Nucleosome Occupancy and Methylation sequencing (NOMe-seq) to compare the genome-wide DNA methylation and nucleosome occupancy profiles between normal and cancer cell line models of the breast and prostate. Here we describe the bioinformatic pipeline and methods that we developed for the processing and analysis of the NOMe-seq data published by (Taberlay et al., 2014 [1]) and deposited in the Gene Expression Omnibus with accession GSE57498.
Keywords	DNA ; DNA methylation ; bioinformatics ; breasts ; carcinogenesis ; epigenetics ; gene expression ; genes ; human cell lines ; models ; neoplasms ; nucleosomes
Language	English
Dates of publication	2015-03
Size	p. 94-96.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2751131-5
ISSN	2213-5960
ISSN	2213-5960
DOI	10.1016/j.gdata.2014.11.012
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Epigenetic modifications as therapeutic targets.

Kelly, Theresa K / De Carvalho, Daniel D / Jones, Peter A

Nature biotechnology

2010 Volume 28, Issue 10, Page(s) 1069–1078

Abstract: Epigenetic modifications work in concert with genetic mechanisms to regulate transcriptional activity in normal tissues and are often dysregulated in disease. Although they are somatically heritable, modifications of DNA and histones are also reversible, ...

Abstract	Epigenetic modifications work in concert with genetic mechanisms to regulate transcriptional activity in normal tissues and are often dysregulated in disease. Although they are somatically heritable, modifications of DNA and histones are also reversible, making them good targets for therapeutic intervention. Epigenetic changes often precede disease pathology, making them valuable diagnostic indicators for disease risk or prognostic indicators for disease progression. Several inhibitors of histone deacetylation or DNA methylation are approved for hematological malignancies by the US Food and Drug Administration and have been in clinical use for several years. More recently, histone methylation and microRNA expression have gained attention as potential therapeutic targets. The presence of multiple epigenetic aberrations within malignant tissue and the abilities of cells to develop resistance suggest that epigenetic therapies are most beneficial when combined with other anticancer strategies, such as signal transduction inhibitors or cytotoxic treatments. A key challenge for future epigenetic therapies will be to develop inhibitors with specificity to particular regions of chromosomes, thereby potentially reducing side effects.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; DNA Methylation/drug effects ; Epigenesis, Genetic/drug effects ; Histone Deacetylase Inhibitors/therapeutic use ; Histones/metabolism ; Humans ; Neoplasms/drug therapy ; Nucleosides/therapeutic use
Chemical Substances	Antineoplastic Agents ; Histone Deacetylase Inhibitors ; Histones ; Nucleosides
Language	English
Publishing date	2010-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1311932-1
ISSN	1546-1696 ; 1087-0156
ISSN (online)	1546-1696
ISSN	1087-0156
DOI	10.1038/nbt.1678
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Zs.A 2167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 137: Show issues
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Article ; Online: Methylation-sensitive single-molecule analysis of chromatin structure.

Miranda, Tina B / Kelly, Theresa K / Bouazoune, Karim / Jones, Peter A

Current protocols in molecular biology

2010 Volume Chapter 21, Page(s) Unit 21.17.1–16

Abstract: Methylation-sensitive single-molecule analysis of chromatin structure is a high-resolution method for studying nucleosome positioning. As described in this unit, this method allows for the analysis of the chromatin structure of unmethylated CpG islands ... ...

Abstract	Methylation-sensitive single-molecule analysis of chromatin structure is a high-resolution method for studying nucleosome positioning. As described in this unit, this method allows for the analysis of the chromatin structure of unmethylated CpG islands or in vitro-remodeled nucleosomes by treatment with the CpG-specific DNA methyltransferase SssI (M.SssI), followed by bisulfite sequencing of individual progeny DNA molecules. Unlike nuclease-based approaches, this method allows each molecule to be viewed as an individual entity instead of an average population.
MeSH term(s)	Animals ; Biocatalysis ; Chromatin/chemistry ; CpG Islands ; DNA Methylation ; Genetic Techniques ; Humans
Chemical Substances	Chromatin
Language	English
Publishing date	2010-01
Publishing country	United States
Document type	Journal Article
ISSN	1934-3647
ISSN (online)	1934-3647
DOI	10.1002/0471142727.mb2117s89
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