A tissue-specific transcriptional enhancer is found in the body of the HLA-DR alpha gene.

Wang, Yao; Larsen, A. S.; Peterlin, B. Matija

doi:10.1084/jem.166.3.625

Cited by 32 publications

(14 citation statements)

References 29 publications

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“…Class II gene expression is under trans-regulatory control by a number of protein factors which interact with sequences immediately upstream of the origin of transcription (reviewed in reference 52). The role of downstream elements in the expression of MHC genes, however, is not understood (15,29,39,53,62), so any possible significance of our findings to E, transcriptional regulation is unknown.…”

Section: Resultsmentioning

confidence: 65%

DNase I-hypersensitive sites and transcription factor-binding motifs within the mouse E beta meiotic recombination hot spot.

1991

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The frequency of meiotic and mitotic recombination is not uniform throughout a chromosome. Eucaryotic recombination hot spots have been well characterized in a number of species including mice (4, 8, 23-25, 40, 49, 50, 58, 59) and fungi (reviewed in reference 37). However, only limited information exists on the molecular mechanisms by which hot spots enhance homologous recombination. Intrachromosomal somatic recombination mediated by variable-diversity-joining region [V(D)J] recombinase leads to immunoglobulin and T-cell receptor gene rearrangements. Plasmid constructs have been used to show that VDJ recombination events are stimulated by transcription. This observation led to the idea that enhanced DNA accessibility potentiates genetic exchange (5, 6). Repeated sequences capable of forming Z DNA and a human minisatellite sequence have been found to enhance recombination in yeast and mammalian cell culture systems, but the molecular mechanism for the effect is unknown (7,9,51,57,61). Studies on mitotic recombination indicate that genetic exchange in yeast cells, can be stimulated by transcription (55, 60), but recent studies (44) on a hot spot active in yeast meiosis (36,54) show that transcription is not necessary for hot-spot activity.Unfortunately, experimental systems that simulate the conditions of meiosis in higher eucaryotes are unavailable, and therefore the molecular basis of meiotic-recombination hot spots in these organisms is obscure. Stimulated by the suggestion that recombination enhancement might result from increased accessibility of DNA sequences to the cell's recombination machinery, we decided to determine the state of DNA accessibility in one of the best-defined mammalian meiotic-recombination hot spots (4,8,23,40,49). This hot spot is found in the second intron of the class II E3 gene in the mouse major histocompatibility complex (MHC). Although mouse class II genes are spread out over more than 300 kb, recombination in most crosses between inbred strains is limited to an approximately 3-kb region in the second E,B intron. In our studies we analyzed the chromatin conformation in this gene segment in somatic cells and in purified meiotic pachytene cells isolated from mouse testes.

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Section: Resultsmentioning

confidence: 65%

DNase I-hypersensitive sites and transcription factor-binding motifs within the mouse E beta meiotic recombination hot spot.

1991

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“…Jurkat T cells were maintained in RPMI 1640 with 10% fetal bovine serum (RF-10) and transfected using DEAE-dextran according to the method of Wang et al (1987) with the following modifications: 1) 107 cells were used per sample; 2) the chloroquine shock step was limited to 10 min and carried out after the addition of 7.5 ml of prewarmed RPMI 1640/5% fetal bovine serum to the cells, DNA, and DEAE-dextran; and 3) after the chloroquine treatment, the cells were centrifuged at 1000 rpm and 4°C for 5 min (Beckman GS-6R centrifuge), and after removal of the last drops of supernatant with a transfer pipette were directly resuspended in RF-10. Five micrograms of reporter construct were used per sample, along with 2.5 jig of pHtat,, pBOSEtsl, pBOSElfl, or pEFBOS as appropriate.…”

Section: Methodsmentioning

confidence: 99%

The nfkb1 promoter is controlled by proteins of the Ets family.

Lambert

Ludford-Menting

Deacon

et al. 1997

MBoC

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The gene encoding NFKB1 is autoregulated, responding to NF-KB/Rel activation through NF-KB binding sites in its promoter, which also contains putative sites for Ets proteins. One of the Ets sites, which we refer to as EBS4, is located next to an NF-KB/Rel binding site, kB3, which is absolutely required for activity of the promoter in Jurkat T cells in response to activation by phorbol 12-myristate 13-acetate (PMA), PMA/ionomycin, or the Tax protein from human T cell leukemia virus type I. We show that EBS4 is required for the full response of the nfkbl promoter to PMA or PMA/ionomycin in Jurkat cells. EBS4 is bound by Ets-1, Elf-1, and other species. Overexpression of Ets-1 augments the response to PMA/ionomycin and this is reduced by mutation of EBS4. Elf-1 has less effect in conjunction with PMA/ionomycin, but by itself activates the promoter 12-fold. This activation is only partly affected by mutation of EBS4, and a mutant promoter that binds Ets-1, but not Elf-1, at the EBS4 site responds to PMA/ionomycin as efficiently as the wild-type. Ets proteins may be responsible for fine-tuning the activity of the nfkbl gene in a cell-type-specific manner.

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“…Expression vectors for various NF-KB subunits (14,19,20) were transfected with a threefold molar excess of the precursor plasmids. Transient transfection of the Jurkat T-cell line was performed by a modification of the DEAEdextran technique (48). At approximately 48 h after transfection, cells were harvested and extracts were prepared as described previously (20).…”

Section: Methodsmentioning

confidence: 99%

Alternate RNA splicing of murine nfkb1 generates a nuclear isoform of the p50 precursor NF-kappa B1 that can function as a transactivator of NF-kappa B-regulated transcription.

Grumont¹,

Fecondo²,

Gerondakis³

1994

Mol. Cell. Biol.

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The NF-KB1 subunit of the transcription factor NF-KB is derived by proteolytic cleavage from the N terminus of a 105-kDa precursor protein. The C terminus of p1O5NF-KBI, like those of IKB proteins, contains ankyrin-related repeats that inhibit DNA binding and nuclear localization of the precursor and confer IKB-like properties upon p1O5NF-KB1. Here we report the characterization of two novel NF-KB1 precursor isoforms, p84NF-KB1 and p98NF-KBI, that arise by alternate splicing within the C-terminal coding region of murine njkbl. p98NF-KB1, which lacks the 111 C-terminal amino acids (aa) of p1O5NF-KBl, has a novel 35-aa C terminus encoded by an alternate reading frame of the gene. p84NF-KB1 lacks the C-terminal 190 aa of p1O5NF-KB1, including part of ankyrin repeat 7. RNA and protein analyses indicated that the expression of p84NF-KB1 and p98NF-KB1 is restricted to certain tissues and that the phorbol myristate acetate-mediated induction of p84NF-KB1 and p1O5NF-KB1 differs in a cell-type-specific manner. Both p84NF-KB1 and p98NF-KB1 are found in the nuclei of transfected cells. Transient transfection analysis revealed that p98NF-KB1, but not p1O5NF-KBl or p84NF-KBI, acts as a transactivator of NF-KB-regulated gene expression and that this is dependent on sequences in the Rel homology domain required for DNA binding and on the novel 35 C-terminal aa of this isoform. In contrast to previous findings, which indicated that p1O5NF-KB1 does not bind DNA, all of the NF-KB1 precursors were found to specifically bind with low alfinity to a highly restricted set of NF-KB sites in vitro, thereby raising the possibility that certain of the NF-.cBl precursor isoforms may directly modulate gene expression.The NF-KB-like transcription factors comprise a group of homodimeric and heterodimeric proteins, all the subunits of which are encoded by a small multigene family related to the v-rel oncogene (1,6,17,38). The best characterized of these factors, NF-KB, comprises a heterodimer of 50-kDa (p5O) and 65-kDa (p65) proteins. NF-KB binds to decameric sequences conforming to the motif GGGARNNYYCC (KB site) found within the promoters and enhancers of viral genes and cellular genes (1,26). In most cell types, NF-KB-like proteins are found in the cytoplasm in a non-DNA-binding form, associated with a family of regulatory proteins termed inhibitors (IKBs) (1,6,17). The cytoplasmic form of NF-KB is activated by a wide range of extracellular signals which lead to the phosphorylation of IKB (15, 27) and its dissociation from NF-KB and subsequent degradation (10, 21), thereby allowing NF-KB to be translocated to the nucleus.In mammals, five different genes encoding proteins homologous to the v-rel oncoprotein have been identified. p65 (RelA), RelB, p52/plOO(NF-KB2), p50/p105(NF-KB1), and the product of the c-rel proto-oncogene all share a highly conserved domain of approximately 300 amino acids termed the Rel homology domain that is located in the amino-terminal halves of these proteins. The Rel homology domain contains sequences important for...

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A tissue-specific transcriptional enhancer is found in the body of the HLA-DR alpha gene.

Cited by 32 publications

References 29 publications

DNase I-hypersensitive sites and transcription factor-binding motifs within the mouse E beta meiotic recombination hot spot.

DNase I-hypersensitive sites and transcription factor-binding motifs within the mouse E beta meiotic recombination hot spot.

The nfkb1 promoter is controlled by proteins of the Ets family.

Alternate RNA splicing of murine nfkb1 generates a nuclear isoform of the p50 precursor NF-kappa B1 that can function as a transactivator of NF-kappa B-regulated transcription.

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