Position-dependent variegation of globin transgene expression in mice.

Robertson, Graham; Garrick, David; Wu, Wenlian; Kearns, Margot; Martin, David I. K.; Whitelaw, Emma

doi:10.1073/pnas.92.12.5371

Cited by 155 publications

(112 citation statements)

References 25 publications

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…Robertson et al (1995) described the silencing of expression of a construct containing an Escherichia coli lacZ gene under control of the human ~-globin HS-40 element in transgenic mice. It had been shown previously that HS-40 could not maintain highlevel copy number-dependent expression of the c~-globin gene throughout development as expression levels declined as development proceeded (Sharpe et al 1992(Sharpe et al , 1993.…”

Section: Modulation Of Gene Expressionmentioning

confidence: 99%

The role of EKLF in human beta-globin gene competition.

Wijgerde

Gribnau²,

Trimborn³

et al. 1996

Genes Dev.

197

242

View full text Add to dashboard Cite

We have investigated the role of erythroid Kruppel-like factor (EKLF) in expression of the human 13-globin genes in compound EKLF knockout/human I~-locus transgenic mice. EKLF affects only the adult mouse 13-globin genes in homozygous knockout mice; heterozygous mice are unaffected. Here we show that EKLF knockout mice express the human e and 7-globin genes normally in embryonic red cells. However, fetal liver erythropoiesis, which is marked by a period of 7" and 13-gene competition in which the genes are alternately transcribed, exhibits an altered ratio of 7" to 13-gene transcription. EKLF heterozygous fetal livers display a decrease in the number of transcriptionally active 13 genes with a reciprocal increase in the number of transcriptionally active 7 genes. 13-gene transcription is absent in homozygous knockout fetuses with coincident changes in chromatin structure at the 13 promoter. There is a further increase in the number of transcriptionally active 7 genes and accompanying 7 gene promoter chromatin alterations. These results indicate that EKLF plays a major role in 7-and I~-gene competition and suggest that EKLF is important in stabilizing the interaction between the Locus Control Region and the 13-globin gene. In addition, these findings provide further evidence that developmental modulation of globin gene expression within individual cells is accomplished by altering the frequency and/or duration of transcriptional periods of a gene rather than changing the rate of transcription.

show abstract

Section: Modulation Of Gene Expressionmentioning

confidence: 99%

The role of EKLF in human beta-globin gene competition.

Wijgerde

Gribnau²,

Trimborn³

et al. 1996

Genes Dev.

197

242

View full text Add to dashboard Cite

show abstract

“…Human ␣-globin genes are clustered on a single complex located in the telomeric region of the short arm of chromosome 16. This complex includes three functional genes, the embryonic 2 gene and the two fetal/adult ␣2 and ␣1 genes, which are arranged in the order 5Ј-2-␣2-␣1-3Ј of their expression during development (1).…”

mentioning

confidence: 99%

Non-erythroid Genes Inserted on Either Side of Human HS-40 Impair the Activation of Its Natural α-Globin Gene Targets without Being Themselves Preferentially Activated

Espéret

Sabatier

Deville

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

The human ␣-globin gene complex includes three functional globin genes (5-2-␣2-␣1-3) regulated by a common positive regulatory element named HS-40 displaying strong erythroid-specific enhancer activity. How this enhancer activity can be shared between different promoters present at different positions in the same complex is poorly understood. To address this question, we used homologous recombination to target the insertion of marker genes driven by cytomegalovirus or long terminal repeat promoters in both possible orientations either upstream or downstream from the HS-40 region into the single human ␣-globin gene locus present in hybrid mouse erythroleukemia cells. We also used CRE recombinase-mediated cassette exchange to target the insertion of a tagged ␣-globin gene at the same position downstream from HS-40. All these insertions led to a similar decrease in the HS-40-dependent transcription of downstream human ␣-globin genes in differentiated cells. Interestingly, this decrease is associated with the strong activation of the proximal newly inserted ␣-globin gene, whereas in marked contrast, the transcription of the non-erythroid marker genes remains insensitive to HS-40. Taken together, these results indicate that the enhancer activity of HS-40 can be trapped by non-erythroid promoters in both upstream and downstream directions without necessarily leading to their own activation.Human ␣-globin genes are clustered on a single complex located in the telomeric region of the short arm of chromosome 16. This complex includes three functional genes, the embryonic 2 gene and the two fetal/adult ␣2 and ␣1 genes, which are arranged in the order 5Ј-2-␣2-

show abstract

“…This has been discussed by Feng et al to account for the rather extreme variability in reporting Thy1 expression in twenty-five transgenic lines (Feng et al, 2000). Transgene expression can also be affected by the number of copies of the transgene that have become integrated, the site of chromosomal integration or other factors such as position effect variegation (see: Dorer and Henikoff, 1997;Garrick et al, 1998;Robertson et al, 1995;Sabl and Henikoff, 1996) . The difference in expression is not accompanied by any aberration in development as both transgenic lines develop normally and no YFP-induced toxicities are found.…”

Section: Discussionmentioning

confidence: 99%

A transgenic mouse Class‐III β tubulin reporter using yellow fluorescent protein

Liu

Geisert

Frankfurter

et al. 2007

Genesis

View full text Add to dashboard Cite

A yellow fluorescence protein (YFP) reporter construct was cloned downstream of the β-tubulin III promoter and injected to produce two founder lines of transgenic mice. YFP expression was observed in many regions of the developing peripheral and central nervous system. YFP expression was first observed in the peripheral and central nervous system as early as embryonic day 9.0. There was a dramatic increase in the number of neuronal systems expressing YFP through P0. Then as the animals reached adult age the expression levels decreased, but many neurons still show YFP expression, noteably in regions of the brain undergoing adult neurogenesis, i.e., the rostral migratory stream and sub-granular layer of the dentate gyrus. This reporter-based staining was compared with anti-class-III β-tubulin immunocytochemistry and shown to closely parallel the expression of the endogenous protein. These transgenic lines should provide unique models to study in vivo and in vitro neurodevelopment.

show abstract

Position-dependent variegation of globin transgene expression in mice.

Cited by 155 publications

References 25 publications

The role of EKLF in human beta-globin gene competition.

The role of EKLF in human beta-globin gene competition.

Non-erythroid Genes Inserted on Either Side of Human HS-40 Impair the Activation of Its Natural α-Globin Gene Targets without Being Themselves Preferentially Activated

A transgenic mouse Class‐III β tubulin reporter using yellow fluorescent protein

Contact Info

Product

Resources

About