Linked Life Data

17641388

Source:http://linkedlifedata.com/resource/pubmed/id/17641388

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-10-8
pubmed:abstractText
Complex organisms contain a variety of distinct cell types but only a single genome. Therefore, cellular identity must be specified by the developmentally regulated expression of a subset of genes from an otherwise static genome. In mammals, genomic DNA is modified by cytosine methylation, resulting in a pattern that is distinctive for each cell type (the epigenome). Because nucleosomal histones are subject to a wide variety of post-translational modifications (PTMs), we reasoned that an analogous "epiproteome" might exist that could also be correlated with cellular identity. Here, we show that the quantitative evaluation of nucleosome PTMs yields epiproteomic signatures that are useful for the investigation of stem cell differentiation, chromatin function, cellular identity, and epigenetic responses to pharmacologic agents. We have developed a novel enzyme-linked immunosorbent assay-based method for the quantitative evaluation of the steady-state levels of PTMs and histone variants in preparations of native intact nucleosomes. We show that epiproteomic responses to the histone deacetylase inhibitor trichostatin A trigger changes in histone methylation as well as acetylation, and that the epiproteomic responses differ between mouse embryonic stem cells and mouse embryonic fibroblasts (MEFs). ESCs subjected to retinoic acid-induced differentiation contain reconfigured nucleosomes that include increased content of the histone variant macroH2A and other changes. Furthermore, ESCs can be distinguished from embryonal carcinoma cells and MEFs based purely on their epiproteomic signatures. These results indicate that epiproteomic nucleosomal signatures are useful for the investigation of stem cell identity and differentiation, nuclear reprogramming, epigenetic regulation, chromatin dynamics, and assays for compounds with epigenetic activities. Disclosure of potential conflicts of interest is found at the end of this article.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1549-4918
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2567-74
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17641388-Acetylation, pubmed-meshheading:17641388-Animals, pubmed-meshheading:17641388-Biological Markers, pubmed-meshheading:17641388-Cell Differentiation, pubmed-meshheading:17641388-Cells, Cultured, pubmed-meshheading:17641388-Embryonic Stem Cells, pubmed-meshheading:17641388-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:17641388-Fibroblasts, pubmed-meshheading:17641388-Gene Expression Regulation, Developmental, pubmed-meshheading:17641388-Histone Deacetylase Inhibitors, pubmed-meshheading:17641388-Histones, pubmed-meshheading:17641388-Hydroxamic Acids, pubmed-meshheading:17641388-Methylation, pubmed-meshheading:17641388-Mice, pubmed-meshheading:17641388-Nucleosomes, pubmed-meshheading:17641388-Pluripotent Stem Cells, pubmed-meshheading:17641388-Protein Processing, Post-Translational, pubmed-meshheading:17641388-Proteomics, pubmed-meshheading:17641388-Tretinoin
pubmed:year
2007
pubmed:articleTitle
Global epiproteomic signatures distinguish embryonic stem cells from differentiated cells.
pubmed:affiliation
Center for Regenerative Biology, University of Connecticut, Storrs, Connecticut 06269-4243, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural