Linked Life Data

8298193

Source:http://linkedlifedata.com/resource/pubmed/id/8298193

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1994-3-10
pubmed:abstractText
Transgenic mice have been used extensively to study elements governing the erythroid-specific developmental switch from human fetal gamma to human adult beta globin. Previous work demonstrated that a small construct composed of hypersensitive site 2 (HS2) of the locus control region (LCR) linked to the gamma and beta globin genes (HS2-gamma-beta) is sufficient for correct tissue and temporal expression of these genes, whereas HS2-beta alone is inappropriately expressed in the embryo. Two models, which are not mutually exclusive, have been proposed to explain these results and those of other constructs in transgenic mice. One model emphasizes the conserved polarity in the globin locus and suggests a distance effect whereby the beta globin gene must be removed from the LCR/HS2 to prevent an early and incorrect activation of this gene in the embryonic compartment. A second hypothesis proposes a competition between the gamma and beta globin gene promoters for interaction with the LCR/HS2. The active gamma globin gene promoter positioned between the LCR/HS2 and the beta globin gene thereby interacts with the HS2 elements early in erythroid development and is expressed until a change in putative stage-specific nuclear factors makes an interaction with the adult beta globin gene more favorable. In an effort to test the competition model, a construct has been prepared in which a small deletion was produced in the promoter region of the gamma globin gene while in the context of the HS2-gamma-beta plasmid. Analysis of this construct in transgenic mice reveals a constitutive unregulated expression of the human beta globin gene during erythroid development. To determine if this competition effect is specific for globin genes, a heterologous reporter gene has been substituted for the gamma globin gene in the construct HS2-gamma-beta. In this case, the beta globin gene exhibits correct developmental expression. This data is consistent with a model in which transcription from a promoter upstream of the beta globin gene in some manner protects this adult gene from activation by the LCR/HS2 during early development.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-1373805, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-1549112, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-1639067, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-1692558, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-1706482, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-1714415, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2000371, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2216720, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2295312, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2314472, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2357964, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2362805, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2476809, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2721958, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2828925, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2922063, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2924354, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-2992937, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-3039464, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-3456593, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-3478680, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-3690667, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-3868484, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-3879975, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-3951540, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-6205403, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-6269744, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-6397774, http://linkedlifedata.com/resource/pubmed/commentcorrection/8298193-6960240
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1059-1524
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1077-85
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Regulated expression of the human beta globin gene in transgenic mice requires an upstream globin or nonglobin promoter.
pubmed:affiliation
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Ohio 45267-0524.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.