scholarly journals Deletion analysis of the human CD2 gene locus control region in transgenic mice

1991 ◽  
Vol 19 (21) ◽  
pp. 5851-5856 ◽  
Author(s):  
Georgina Lang ◽  
Clio Mamalaki ◽  
David Greenberg ◽  
Nicholas Yannoutsos ◽  
Dimitris Kioussis
Keyword(s):  
Transgenic Mice ◽  
Control Region ◽  
Gene Locus ◽  
Locus Control Region ◽  
Deletion Analysis

Position independence and proper developmental control of gamma-globin gene expression require both a 5' locus control region and a downstream sequence element

1994 ◽  
Vol 14 (9) ◽  
pp. 6087-6096
Author(s):  
Q Li ◽  
J A Stamatoyannopoulos
Keyword(s):  
Transgenic Mice ◽  
Control Region ◽  
Locus Control Region ◽  
Regulatory Sequences ◽  
Globin Genes ◽  
Sequence Element ◽  
Position Effects ◽  
Developmental Control ◽  
Developmental Patterns ◽  
Gamma Globin

We have analyzed the expression of human gamma-globin genes during development in F2 progeny of transgenic mice carrying two types of constructs. In the first type, gamma-globin genes were linked individually to large (approximately 4-kb) sequence fragments spanning locus control region (LCR) hypersensitive site 2 (HS2) or HS3. These LCR fragments contained not only the core HS elements but also extensive evolutionarily conserved flanking sequences. The second type of construct contained tandem gamma- and beta-globin genes linked to identical HS2 or HS3 fragments. We show that gamma-globin expression in transgenic mice carrying HS2 gamma or HS3 gamma constructs is highly sensitive to position effects and that such effects override the cis regulatory elements present in these constructs to produce markedly different developmental patterns of gamma-globin expression in lines carrying the same transgene. In contrast, gamma-globin expression in both HS2 gamma beta and HS3 gamma beta mice is sheltered from position effects and the developmental patterns of gamma-globin expression in lines carrying the same transgene are identical and display stage-specific regulation. The results suggest that cis regulatory sequences required for proper developmental control of fetal globin expression in the presence of an LCR element reside downstream from the gamma genes.

scholarly journals The beta-globin locus control region enhances transcription of but does not confer position-independent expression onto the lacZ gene in transgenic mice.

1996 ◽  
Vol 15 (14) ◽  
pp. 3713-3721 ◽  
Author(s):  
L. G. Guy ◽  
R. Kothary ◽  
Y. DeRepentigny ◽  
N. Delvoye ◽  
J. Ellis ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Control Region ◽  
Locus Control Region ◽  
Lacz Gene ◽  
Beta Globin

scholarly journals Locus control region-A gamma transgenic mice: a new model for studying the induction of fetal hemoglobin in the adult

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1326-1333 ◽  
Author(s):  
P Constantoulakis ◽  
B Josephson ◽  
L Mangahas ◽  
T Papayannopoulou ◽  
T Enver ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Control Region ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Locus Control Region ◽  
In Vivo Studies ◽  
Regulatory Sequences ◽  
Mouse Development ◽  
New Model ◽  
Gamma Globin

Abstract All pharmacologic agents that induce fetal hemoglobin (Hb) have been discovered with in vivo studies of humans, macaques, and baboons. We tested whether transgenic mice carrying human fetal (gamma) globin genes provide a model for studying the pharmacologic induction of HbF in the adult. In initial studies, phenylhydrazine-induced hemolytic anemia, 5-azacytidine, butyrate, or combinations of these treatments failed to activate the human gamma-globin gene in a transgenic mouse line carrying a 4.4-kb G gamma globin gene construct that is expressed only in the embryonic stage of mouse development. Subsequently, adult mice carrying the human A gamma gene linked to the locus control region (LCR) regulatory sequences and expressing heterocellularly HbF (about 25%, gamma-positive cells) were used. Treatments with erythropoietin, 5- azacytidine, hydroxyurea, or butyrate resulted in induction of gamma gene expression as documented by measurement of F-reticulocytes, the gamma/gamma + beta biosynthetic ratio and the level of steady state gamma mRNA. Administration of erythropoietin or butyrate to transgenic mice carrying a muLCR-beta (human) globin construct, failed to increase human beta-globin expression. These results suggest that the muLCR-A gamma transgenic mice provide a new model for studying the induction of fetal Hb in the adult.

A Novel Deletion/Insertion Caused by a Replication Error in the β-Globin Gene Locus Control Region

Hemoglobin ◽  
2011 ◽  
Vol 35 (4) ◽  
pp. 316-322 ◽  
Author(s):  
Philippe Joly ◽  
Philippe Lacan ◽  
Caroline Garcia ◽  
Roland Meley ◽  
Corinne Pondarré ◽  
...  
Keyword(s):  
Control Region ◽  
Gene Locus ◽  
Globin Gene ◽  
Locus Control Region ◽  
Replication Error

scholarly journals Human beta-globin locus control region: analysis of the 5' DNase I hypersensitive site HS 2 in transgenic mice.

1991 ◽  
Vol 88 (5) ◽  
pp. 1626-1630 ◽  
Author(s):  
J. J. Caterina ◽  
T. M. Ryan ◽  
K. M. Pawlik ◽  
R. D. Palmiter ◽  
R. L. Brinster ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Control Region ◽  
Locus Control Region ◽  
Dnase I ◽  
Beta Globin ◽  
Hypersensitive Site ◽  
Region Analysis ◽  
Dnase I Hypersensitive Site

scholarly journals Sheltering of gamma-globin expression from position effects requires both an upstream locus control region and a regulatory element 3' to the A gamma-globin gene.

1997 ◽  
Vol 17 (1) ◽  
pp. 240-247 ◽  
Author(s):  
J A Stamatoyannopoulos ◽  
C H Clegg ◽  
Q Li
Keyword(s):  
Transgenic Mice ◽  
Control Region ◽  
Regulatory Element ◽  
Globin Gene ◽  
Locus Control Region ◽  
Regulatory Elements ◽  
Sequence Information ◽  
Hindiii Site ◽  
Position Effects ◽  
Gamma Globin

Integration position-independent expression of human globin transgenes in transgenic mice requires the presence of regulatory elements from the beta-globin locus control region (LCR) in the transgene construct. However, several recent studies have suggested that, while clearly necessary, such elements are not by themselves sufficient to realize this effect. In the case of the human fetal gamma-globin genes, previous results have indicated that additional regulatory information required for sheltering of gamma-globin transgene expression from position effects may reside downstream from the A gamma gene. To investigate this possibility, we established 17 lines of transgenic mice carrying constructs comprising a micro-LCR (microLCR) element, an A gamma-globin gene fragment, and a variable length of 3' sequence information beyond the A gamma 3' HindIII site. gamma-Globin expression during development was studied in 170 individual F2 progeny from these lines. We find that gamma-globin expression becomes sheltered from position effects when the normally position-sensitive microLCR-A gamma construct is extended by 600 bp beyond the 3' HindIII site to include a previously identified regulatory sequence (the A gamma-globin enhancer), the functional significance of which in vivo had heretofore been unclear. The results suggest that the mechanism whereby an upstream LCR achieves sheltering of globin gene expression from position effects involves cooperation with a gene-proximal regulatory element distinct from the promoter region.

scholarly journals Function and Factor Interactions of a Locus Control Region Element in the Mouse T Cell Receptor-α/Dad1 Gene Locus

2001 ◽  
Vol 167 (7) ◽  
pp. 3836-3845 ◽  
Author(s):  
Benjamin D. Ortiz ◽  
Faith Harrow ◽  
Dragana Cado ◽  
Buyung Santoso ◽  
Astar Winoto
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Control Region ◽  
Gene Locus ◽  
Locus Control Region ◽  
Cell Receptor ◽  
Factor Interactions
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