Cis-acting sequences regulating expression of the human α-globin cluster lie within constitutively open chromatin

Vyas, Paresh; Vickers, Mark A.; Simmons, David L.; Ayyub, Helena; Craddock, Charles; Higgs, Deborah

doi:10.1016/0092-8674(92)90290-s

Cited by 156 publications

(122 citation statements)

References 75 publications

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“…The coordinated regulation of several genes by a distal regulatory element has been illustrated before with the 3-globin locus control region (19). An analysis of the a-globin locus has also revealed the presence of many linked transcripts (60). Future experiments in our laboratory will address this question and could potentially reveal a locus of coordinately transcribed genes.…”

Section: Discussionmentioning

confidence: 99%

Elf-1 binds to a critical element in a second CD4 enhancer.

Wurster¹,

Siu²,

Leiden³

et al. 1994

Mol. Cell. Biol.

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The coordinated expression of CD4 and CD8 during T-cell development is tightly coupled with the maturation state of the T cell. Additionally, the mutually exclusive expression of these receptors in mature T cells is representative of the functional T-cell subclasses (CD4+ helper T cells versus CD8+ cytotoxic T cells). We have studied the regulation CD4 gene transcription during T-cell development in an attempt to gain an understanding of the molecular mechanisms involved in T-cell development and differentiation. Here we present the identification of a second transcriptional enhancer in the murine CD4 locus 24 kb upstream of the CD4 promoter. This enhancer is active in mature T cells and is especially active in CD4+ helper T cells. A number of nuclear proteins bind to elements in the minimal CD4 enhancer that includes consensus sites for AP-1, Spl, Gata, and Ets transcription factor families. We find that the Ets consensus site is crucial for enhancer activity and that the recently identified Ets factor, Elf-i, which is expressed at high levels in T cells and involved in the regulation of several other T-cell-specific genes, is a dominant protein in T-cell nuclear extracts that binds to this site.T-cell development involves the differentiation of functionally immature pre-T cells into mature, antigen-reactive effector cells (reviewed in reference 61). This process includes selection events in which the maturing T-cell population is depleted of self-reactive clones and enriched for those that can recognize foreign peptides bound by self-major histocompatibility complex (MHC). The development and selection of T-cell precursors occur in the thymus and are characterized by a coordinated expression of tissue-specific genes. Some of these genes encode cell surface molecules that directly promote T-cell differentiation and selection events. Understanding the molecular mechanisms responsible for the expression of these T-cellspecific genes is a window on the process of T-cell development.The CD4 glycoprotein is one of the surface molecules that is important as a receptor in the development and function of T cells (reviewed in references 39 and 46). In mature antigenspecific T cells, CD4 is expressed only on cells that have a T-cell receptor (TCR) specific for antigen associated with class II MHC molecules, while CD8, a cell surface protein functionally similar to CD4, is expressed only on T cells that recognize antigen bound to MHC class I molecules (56). The mutually exclusive expression of CD4 and CD8 on mature T cells also corresponds to T-cell function; CD4 is expressed primarily on helper T cells, while CD8 is expressed on cytotoxic T cells. CD4 participates in antigen recognition by binding to nonpolymorphic regions of class II MHC molecules, while the T-cell antigen receptor recognizes a specific peptide antigen that is bound by the MHC molecule (7). The CD4-MHC interaction serves to increase the avidity of the T cell to the antigenpresenting cell but also induces an intracellular signaling event through the CD4-...

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Section: Discussionmentioning

confidence: 99%

Elf-1 binds to a critical element in a second CD4 enhancer.

Wurster¹,

Siu²,

Leiden³

et al. 1994

Mol. Cell. Biol.

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“…Although being embedded in markedly different chromosomal environments, both gene clusters display a strictly coordinated pattern of expression during differentiation and development [2,3]. The human α-globin gene cluster includes the α-like globin genes arranged in the order 5′-ζ 2 -ψζ 1 -ψα 2 -ψα 1 -α 2 -α 1 -θ 1 -3′.…”

Section: Introductionmentioning

confidence: 99%

Novel large deletions in the human α-globin gene cluster: Clarifying the HS-40 long-range regulatory role in the native chromosome environment

Coelho

Picanço

Seuanes³

et al. 2010

Blood Cells, Molecules, and Diseases

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“…The LCR may be located within a gene, as is the case for HS-40 (Vyas et al 1992), the growth hormone LCR (Bennani-Baiti et al 1995), and the adenosine deaminase LCR (Aronow et al 1989). In the same way, the intergenic transcripts could also be genic.…”

Section: Transcription Of the Lcr And Intergenic Regionsmentioning

confidence: 99%

“…Some LCRs are directly transcribed by Pol II because of their location in gene introns, and these include HS-40, the LCR-like element in the ␣-globin cluster (Vyas et al 1992), the human growth hormone LCR (Bennani-Baiti et al 1995), and the human adenosine deaminase LCR (Aronow et al 1989). …”

mentioning

confidence: 99%

Intergenic transcription and transinduction of the human β-globin locus

Ashe¹,

Monks²,

Wijgerde³

et al. 1997

Genes Dev.

319

238

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We have identified novel nuclear transcripts in the human ␤-globin locus using nuclear run-on analysis in erythroid cell lines and in situ hybridization analysis of erythroid tissue. These transcripts extend across the LCR and intergenic regions but are undetectable in nonerythroid cells. Surprisingly, transient transfection of a ␤-globin gene (⑀, ␥, or ␤) induces transcription of the LCR and intergenic regions from the chromosomal ␤-globin locus in nonerythroid cell lines. The ␤-globin genes themselves, however, remain transcriptionally silent. Induction is dependent on transcription of the globin gene in the transfected plasmid but does not require protein expression. Using in situ hybridization analysis, we show that the plasmid colocalizes with the endogenous ␤-globin locus providing insight into the mechanism of transinduction.

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Cis-acting sequences regulating expression of the human α-globin cluster lie within constitutively open chromatin

Cited by 156 publications

References 75 publications

Elf-1 binds to a critical element in a second CD4 enhancer.

Elf-1 binds to a critical element in a second CD4 enhancer.

Novel large deletions in the human α-globin gene cluster: Clarifying the HS-40 long-range regulatory role in the native chromosome environment

Intergenic transcription and transinduction of the human β-globin locus

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