Regulation of β-globin gene expression: straightening out the locus

Martin, David I. K.; Fiering, Steven; Groudine, Mark

doi:10.1016/s0959-437x(96)80072-4

Cited by 139 publications

(98 citation statements)

References 57 publications

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“…Based on our comprehensive sequence analysis, we, rather, conclude that proximity determines V␣ rearrangement to genes in the ␦ locus. A similar mechanism is thought to control the transcription of the globin genes that are closest to the locus control region early in development (35). Comparison of our ␦-chain clones expressed in BALB/c mice with their genomic counterparts (see Footnote 5) in all instances revealed a perfect match, with only one exception.…”

Section: Second Wave: Preferential Usage Of the Proximal Cluster Of Dmentioning

confidence: 62%

Vδ Repertoire During Thymic Ontogeny Suggests Three Novel Waves of γδ TCR Expression

Weber-Arden

Wilbert

Kabelitz

et al. 2000

The Journal of Immunology

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Taking advantage of a PCR technique that allows amplification of all variable region genes with equal efficiency, we defined three novel waves of TCR δ-chain transcription during thymic ontogeny. The canonical DV101-D2-J2 rearrangement was confined to a narrow window from days 14 to 18 of gestation, indicating that the postulated two consecutive γδ precursor waves bearing this canonical DV101 rearrangement will coincide on day 16. Neonatal δ-chain transcripts used a second wave of diverse Vα gene segments that are exclusively located in the δ locus-proximal gene cluster of intermingled single members of different Vα subfamilies. In the adult, only expression of a clan of three homologous subfamilies, ADV7, DV104, and ADV17, persists. The members of the ADV7 subfamily are also scattered across the α locus, but their usage does not show the position-dependent bias of the other Vα-to-δ rearrangements.

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Section: Second Wave: Preferential Usage Of the Proximal Cluster Of Dmentioning

confidence: 62%

Vδ Repertoire During Thymic Ontogeny Suggests Three Novel Waves of γδ TCR Expression

Weber-Arden

Wilbert

Kabelitz

et al. 2000

The Journal of Immunology

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“…It was already suspected early on that enhancers and promoters communicate by physical interaction, whereby the intervening DNA is looped out (Figure 3). Evidence supporting such a scenario has steadily increased (Müeller-Storm et al, 1989;Su et al, 1991;Martin et al, 1996). In many cases, enhancer-promoter contacts are stabilized by cohesins, proteins that also play a role in chromosome pairing.…”

Section: Why Activation Over Long Distances?mentioning

confidence: 99%

Enhancers, enhancers – from their discovery to today’s universe of transcription enhancers

Schaffner

2015

Biological Chemistry

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Transcriptional enhancers are short (200-1500 base pairs) DNA segments that are able to dramatically boost transcription from the promoter of a target gene. Originally discovered in simian virus 40 (SV40), a small DNA virus, transcription enhancers were soon also found in immunoglobulin genes and other cellular genes as key determinants of cell-type-specific gene expression. Enhancers can exert their effect over long distances of thousands, even hundreds of thousands of base pairs, either from upstream, downstream, or from within a transcription unit. The number of enhancers in eukaryotic genomes correlates with the complexity of the organism; a typical mammalian gene is likely controlled by several enhancers to fine-tune its expression at different developmental stages, in different cell types and in response to different signaling cues. Here, I provide a personal account of how enhancers were discovered more than 30 years ago, and also address the amazing development of the field since then.

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“…Hence LCR-~ gene interactions, though unchanged in stability, are able to form more frequently. Martin et al (1996)have described a different model of globin gene regulation. They propose that the LCR acts in concert with elements in the locus to initiate and maintain an active chromatin structure.…”

Section: Shifting the Balance Of Globin Gene Competitionmentioning

confidence: 99%

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

Wijgerde

Gribnau²,

Trimborn³

et al. 1996

Genes Dev.

195

241

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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.

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Regulation of β-globin gene expression: straightening out the locus

Cited by 139 publications

References 57 publications

Vδ Repertoire During Thymic Ontogeny Suggests Three Novel Waves of γδ TCR Expression

Vδ Repertoire During Thymic Ontogeny Suggests Three Novel Waves of γδ TCR Expression

Enhancers, enhancers – from their discovery to today’s universe of transcription enhancers

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

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