Linked Life Data

11991750

Source:http://linkedlifedata.com/resource/pubmed/id/11991750

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5 Pt 1
pubmed:dateCreated
2002-5-6
pubmed:abstractText
The expression of integrated oncoretrovirus vectors is subject to the inhibitory effects of surrounding chromatin. A previous report from our laboratory indicated that such position effects can be overcome by flanking a reporter vector with the cHS4 chromatin insulator. To characterize this activity more thoroughly, we switched the promoter-gene combinations in the reporter vector and analyzed expression of these vectors flanked with the cHS4 fragment in both orientations following bone marrow transduction and transplantation in mice. The results indicate that the cHS4 fragment can function in both orientations and can insulate both the virus long-terminal-repeat (LTR) promoter and an internal phosphoglycerate kinase (Pgk) promoter. However, insulation of the LTR promoter diminished when the orientation of the cHS4 fragment placed the CTCF-binding core element immediately proximal to the U3 region, suggesting a minimal distance requirement. Moreover, placement of the cHS4 fragment in the U3 region of the 3' LTR dramatically decreased the level of expression from an internal Pgk promoter, presumably by blocking interaction with the 3' LTR enhancer. Finally, sorting studies suggest that the severity of position effects or autonomous promoter silencing increases as transduced progenitors differentiate into mature progeny. These findings have direct implications for the use of chromatin insulators such as cHS4 in oncoretrovirus vectors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1525-0016
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
589-98
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11991750-3' Untranslated Regions, pubmed-meshheading:11991750-Animals, pubmed-meshheading:11991750-Bone Marrow, pubmed-meshheading:11991750-Bone Marrow Transplantation, pubmed-meshheading:11991750-Cells, Cultured, pubmed-meshheading:11991750-Chickens, pubmed-meshheading:11991750-Chromatin, pubmed-meshheading:11991750-Enhancer Elements, Genetic, pubmed-meshheading:11991750-Gene Expression Regulation, pubmed-meshheading:11991750-Gene Silencing, pubmed-meshheading:11991750-Genetic Vectors, pubmed-meshheading:11991750-Gentamicins, pubmed-meshheading:11991750-Globins, pubmed-meshheading:11991750-Green Fluorescent Proteins, pubmed-meshheading:11991750-Humans, pubmed-meshheading:11991750-Kanamycin Kinase, pubmed-meshheading:11991750-Luminescent Proteins, pubmed-meshheading:11991750-Mice, pubmed-meshheading:11991750-Promoter Regions, Genetic, pubmed-meshheading:11991750-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:11991750-Retroviridae, pubmed-meshheading:11991750-Terminal Repeat Sequences, pubmed-meshheading:11991750-Transduction, Genetic, pubmed-meshheading:11991750-Transgenes
pubmed:year
2002
pubmed:articleTitle
Topological constraints governing the use of the chicken HS4 chromatin insulator in oncoretrovirus vectors.
pubmed:affiliation
Gene and Cell Therapy Center, Hematology Department and Bone Marrow Transplantation Unit, George Papanikolaou General Hospital, Thessaloniki, Greece.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.