Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells.

Ney, Paul A.; Sorrentino, Brian P.; McDonagh, Kevin T.; Nienhuis, Arthur W.

doi:10.1101/gad.4.6.993

Cited by 300 publications

(222 citation statements)

References 80 publications

Supporting

Mentioning

215

Contrasting

Unclassified

Order By: Relevance

“…The possibility of the existence of a common set of initiation sites suggests that specific DNA motifs in HS2 may be capable of initiating the transcription of enhancer RNAs. Indeed, the HS2 sequence has been shown to contain DNA motifs that bind to many transcription factors such as NF-E2 and Ap-1 (33,35,46,48,49), GATA (22,39,49), YY1 (5,12), and USF (4,5,12,40,49). NF-E2, AP-1, and GATA have been suggested to be capable of recruiting and assembling the transcriptional machinery (16,53), and USF and YY1 have been reported to be capable of stimulating transcriptional initiation from their respective binding sites (25,26,41,44).…”

Section: Discussionmentioning

confidence: 99%

Transcription of the HS2 Enhancer toward a cis-Linked Gene Is Independent of the Orientation, Position, and Distance of the Enhancer Relative to the Gene

Kong

Bohl

et al. 1997

Molecular and Cellular Biology

View full text Add to dashboard Cite

The locus control region (LCR) of the human ␤-globin gene domain is defined by four erythroid-cell-specific DNase I-hypersensitive (HS) sites, HS1, -2, -3, and -4, located 50 to 70 kb upstream of the ␤-globin gene in a transcriptional direction: 5Ј HS4-HS3-HS2-HS1-//-ε-G ␥-A ␥-␦-␤ 3Ј (17,20,37,50). The LCR has been shown by studies of natural deletions of ␥␦␤-thalassemia (8,11,24) and by gene transfer experiments (14,18,20,51) to be indispensable for erythroid-cell-specific and high-level transcription of cis-linked globin genes and transgenes. The mechanism by which the LCR regulates transcription of the distant embryonic ε-, fetal ␥-, and adult ␤-globin genes at the respective developmental stages is not fully understood.In previous studies examining the mechanism of LCR function, a number of laboratories have investigated the ability of the individual HS sites to activate the transcription of cislinked genes in cell lines and transgenic mice. Among the LCR HS sites, HS2 has been found to possess developmental-stageindependent enhancer function (52). It is capable of stimulating the transcription of embryonic ε-, fetal ␥-, and adult ␤-globin genes in erythroid cells at the corresponding developmental stages (9,28,34,42,45,47) and may therefore constitute a major functional component of the LCR. However, a recent targeted deletion study shows that deletion of the HS2 enhancer from the murine LCR generated only mild effects on the expression of the ␤-like globin genes (15), suggesting that HS2 is not essential for LCR function and that LCR function may be due to the contribution of the other HS sites. Surprisingly, similar targeted deletion of HS3 also did not cause significant changes in the expression of the ␤-like globin genes (22). These findings suggest that LCR function is due not to the contribution of any specific HS site but to a series of interactions among its functional components, including the enhancer elements underlying the HS sites.In the above-described targeted deletion studies, deleting the HS2 or the HS3 sequence from the endogenous murine LCR and inserting in its place an independent transcription unit-a neomycin-resistant gene driven by a strong promoter-has been found to disrupt LCR function and cause severe anemia in and the deaths of homozygous transgenic mice (15,21). In the human ␤-LCR, inserting an independent transcription unit at a location between the HS2 enhancer and the downstream globin genes also disrupted LCR function (23) and caused the distantly downstream ␤-globin gene to be transcriptionally turned off. The mechanism by which the transcription of a foreign gene within the LCR might disrupt LCR function is not clearly understood (21).In an attempt to delineate the functional mechanism of the HS2 enhancer and ultimately of the LCR, we have previously analyzed the transcriptional status of the HS2 enhancer in transfected recombinant chloramphenicol acetyltransferase (CAT) plasmids (53). This earlier study showed that the transfected HS2 enhancer is itself transcribed in eryt...

show abstract

Section: Discussionmentioning

confidence: 99%

Transcription of the HS2 Enhancer toward a cis-Linked Gene Is Independent of the Orientation, Position, and Distance of the Enhancer Relative to the Gene

Kong

Bohl

et al. 1997

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…On the other hand, site-direct mutagenesis in conjunction with DNA transfection, and transgenic mice studies have demonstrated the essential role of the AP1/NF-E2 motif in the positive as well as negative functioning of several erythroid-speci®c transcriptional regulatory elements (Mignotte et al, 1989;Moi and Kan, 1990;Ney et al, 1990;Talbot and Grosveld, 1991;Huang et al, 1998, and references therein). At the same time, genomic footprinting analysis indicated that the AP1/NF-E2 motifs within several mammalian erythroid-speci®c regulatory elements including the locus-control-region of the human b globin locus or so-called b-globin-LCR (Figure 1), are occupied in vivo by factors in an erythroid lineage and developmental stage speci®c manner (Reddy and Shen, 1991;Ikuta and Kan, 1991;Zhang et al, 1993).…”

Section: Abstract: Chromatin Immunoprecipitation; Ap1; Nf-e2; In Vivomentioning

confidence: 99%

“…Also, both AP1 and NF-E2 are abundantly expressed in K562 cells (Ney et al, 1990;Talbot and Grosveld, 1991). This enhancer consists of two tandemly arranged AP1/NF-E2 motifs with the coding-strand sequence 5'-GCTGAGTCA-3' and 5'-GATGAGTCA-3', respectively.…”

Section: Hs-2 Enhancer Of Human B-globin-lcr Is Bound With Nf-e2 In K562mentioning

confidence: 99%

See 1 more Smart Citation

Distinction between AP1 and NF-E2 factor-binding at specific chromatin regions in mammalian cells

1999

View full text Add to dashboard Cite

Speci®c nuclear factor-DNA complexes formed within the promoters and enhancers are essential for transcriptional regulation. For eukaryotic systems, however, some DNA motif(s) are capable of binding to a family of related factors, thus making it di cult to identify the factor actually binding on the chromatic DNA in vivo and modulating the local transcription processes. To resolve this matter, we have re®ned a chromatin immunoprecipitation assay. Using the assay, we could directly link the regulatory functions of two members of the AP1/NF-E2 transcription factor family and their stable binding in vivo within distinct chromatin regions. The study demonstrated the feasibility of a general scheme in the determination of the identity of speci®c factor(s), among a group of family members, bound at unique sequence(s) in living mammalian cells.

show abstract

“…Individual factor binding sites were then deleted and the mutant HS 2 ,Bglobin constructs were tested in erythroid culture cells (17)(18)(19) or in transgenic mice (20)(21)(22). Deletion of duplicated API-like sites in 5' HS 2 virtually eliminated enhancer activity.…”

Section: Introductionmentioning

confidence: 99%

Cloning and functional characterization of LCR-F1: a bZIP transcription factor that activates erythroid-specific, human globin gene expression

et al. 1994

View full text Add to dashboard Cite

show abstract

Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells.

Cited by 300 publications

References 80 publications

Transcription of the HS2 Enhancer toward a cis-Linked Gene Is Independent of the Orientation, Position, and Distance of the Enhancer Relative to the Gene

Transcription of the HS2 Enhancer toward a cis-Linked Gene Is Independent of the Orientation, Position, and Distance of the Enhancer Relative to the Gene

Distinction between AP1 and NF-E2 factor-binding at specific chromatin regions in mammalian cells

Cloning and functional characterization of LCR-F1: a bZIP transcription factor that activates erythroid-specific, human globin gene expression

Contact Info

Product

Resources

About