Both locus control region and proximal regulatory elements direct the developmental regulation of ?-globin gene cluster

Ji, Xinjun; Liu, De-Pei; Xu, Dongdong; Li, Lei; Wang, Jing; Liang, Chih‐Chuan

doi:10.1002/(sici)1097-4644(20000301)76:3<376::aid-jcb5>3.0.co;2-d

Cited by 5 publications

(7 citation statements)

References 29 publications

(30 reference statements)

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“…The LCR, a cluster of five DNase I hypersensitive sites (HS) located upstream of the 5 0 e-globin gene, is a major cis regulator of all five b-like globin genes (Ji et al 2000;Feng et al 2005). The hypersensitive sites have different roles.…”

Section: Introductionsupporting

confidence: 62%

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Organization of a β and α Globin Gene Set in the Teleost Atlantic Cod, Gadus morhua

Halldórsdóttir

Árnason

2009

Biochem Genet

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Developmental globin gene expression and gene switching in vertebrates have been extensively studied. Globin gene regions have been characterized in some fish species and show linked α and β loci. Understanding coordinated expression between α and β globin genes in fish is of importance for further insights into globin gene regulation in teleosts and higher vertebrates. We characterize linked β and α globin genes in Atlantic cod, pulled from the Atlantic cod genome with a PCR research strategy, by screening a genomic λ library and primer walking. The genes are oriented tail-to-head (5'-3'), differing from the head-to-head orientation in transcriptional polarity characteristic of teleostean globin genes. Four tandem repeats are found in an intergenic region of 1500 base pairs. One microsatellite, which consists primarily of atg tandem repeats, has an open reading frame. The globin genes and open reading frame have a CCAAT promoter element and TATA boxes. The promoters of the open reading frame and the β gene share an 89-bp block (with 100% identity) that probably regulates transcription.

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Section: Introductionsupporting

confidence: 62%

“…The arrangement of the genes in the clusters reflects the order of expression during development. Proximal cis-acting regulatory elements, as well as a distal locus control region (LCR), play a vital role in this regulation (Ji et al 2000;Shen et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Organization of a β and α Globin Gene Set in the Teleost Atlantic Cod, Gadus morhua

Halldórsdóttir

Árnason

2009

Biochem Genet

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“…The looping model states that enhancers and promoters communicate through direct interactions between proteins bound to the DNA elements, with the intervening DNA looping out. This model has been supported by several lines of experimental data (Ji et al 2000;Tolhuis et al 2002).…”

mentioning

confidence: 80%

“…The purified erythroid cells were resuspended in Dulbecco's Modified Eagle Medium (DMEM) media without serum at a cell concentration of 5 × 10 7 /mL (Ji et al 2000).…”

Section: Preparation Of Cell Suspension and Separation Of Nucleated Ementioning

confidence: 99%

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Effect of fetal hemoglobin-stimulating medicines on the interaction of DNA and protein of important erythroid regulatory elements

Liu²,

Xu³

et al. 2003

Biochem. Cell Biol.

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Beta-Thalassemia is the most common single gene disorder in the world, which is caused by the imbalance between alpha-globin chain and beta-globin chain synthesis. Several medicines, such as 5-azacytidine, hydroxyurea, cytarabine, vinblatine, butyrate, and myleran, have been shown to be able to reactivate gamma-globin chain synthesis during the adult stage, and some of them (5-azacytidine, hydroxyurea, myleran, and butyrate) have been used clinically to treat thalassemia and sickle cell disease. Much research efforts are focusing on the determination of the underlying mechanisms of medicine action. In this experiment, as an effort to probe the underlying mechanism of medicine action, we used ligation-mediated polymerase chain reaction and in vivo footprinting methods to study the DNA-protein interaction at critical erythroid regulatory elements after hydroxyurea or myleran administration to mice. Our results showed that the patterns of in vivo footprints at both the hypersensitive site 2 of the locus control region and the beta-globin gene promoter were changed after medicine treatment. We proposed based on these results that the medicines' administration might result in a change in the interaction between trans-acting factors and cis-acting elements at these regions. These changes might influence the assembly of the transcription complex and, lastly, influence the expression of the beta-globin gene.

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The Co-activator p300 Associates Physically with and Can Mediate the Action of the Distal Enhancer of the FGF-4Gene

Nowling

Bernadt

Johnson

et al. 2003

Journal of Biological Chemistry

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Distal enhancers commonly regulate gene expression. However, the mechanisms of transcriptional mediation by distal enhancers remain largely unknown. To better understand distal enhancer-mediated transcription, we examined the regulation of the FGF-4 gene. The FGF-4 gene is regulated during early development by a powerful distal enhancer located downstream of the promoter in exon 3. Sox-2 and Oct-3 bind to the enhancer and are required for the activation of the FGF-4 gene. Previously, we implicated the co-activator p300 as a mediator of Sox-2/Oct-3 synergistic activation of a heterologous promoter, suggesting that p300 may play a role in mediating enhancer activation of the FGF-4 gene. In this study, we provide both functional and physical evidence that p300 plays an important role in the action of the FGF-4 enhancer. Specifically, we show that E1a, but not a mutant form of E1a that is unable to bind p300, inhibits enhancer activation of the FGF-4 promoter. We also demonstrate that Gal4/p300 fusion proteins can stimulate the FGF-4 promoter when bound to the FGF-4 enhancer. Additionally, we present evidence that p300 mediation of the FGF-4 enhancer requires acetyltransferase activity. Importantly, we also show that Sox-2 and p300 are physically associated with the endogenous FGF-4 enhancer but weakly associated with the endogenous FGF-4 promoter. These results are consistent with a model of transitory interaction between the distal enhancer and the FGF-4 promoter. Our results also suggest that intragenic distal enhancers may use mechanisms that differ from extragenic distal enhancers.

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Both locus control region and proximal regulatory elements direct the developmental regulation of ?-globin gene cluster

Cited by 5 publications

References 29 publications

Organization of a β and α Globin Gene Set in the Teleost Atlantic Cod, Gadus morhua

Organization of a β and α Globin Gene Set in the Teleost Atlantic Cod, Gadus morhua

Effect of fetal hemoglobin-stimulating medicines on the interaction of DNA and protein of important erythroid regulatory elements

The Co-activator p300 Associates Physically with and Can Mediate the Action of the Distal Enhancer of the FGF-4Gene

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