Nonhomologous Recombination between the Cytochrome b558Heavy Chain Gene (CYBB) and LINE-1 Causes an X-Linked Chronic Granulomatous Disease

Kumatori, Atsushi; Faizunnessa, Nurun Nahar; Suzuki, Shingo; Moriuchi, Toshiyuki; Kurozumi, Hiroko; Nakamura, Michio

doi:10.1006/geno.1998.5510

Cited by 30 publications

(23 citation statements)

References 35 publications

(37 reference statements)

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“…Homologous recombination events between Alu repeats and between L1 repeats have been reported in 18 (Deininger and Batzer 1999) and 2 cases (Burwinkel and Kilimann 1998;Segal et al 1999) of human disorders, respectively. Non-homologous recombination events involving one of these repeat elements at either end of a recombination site have also been reported in a limited number of mutations (Drechsler and Royer-Pokora 1996;Kumatori et al 1998;Zhang and Zhang 1998;Deininger and Batzer 1999;Morgan et al 1999). As far as we know, examples of recombination events involving the fusion of Alu and L1 repeats have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Non-homologous recombination between Alu and LINE-1 repeats caused a 430-kb deletion in the dystrophin gene: a novel source of genomic instability

et al. 2000

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Although large deletions in the dystrophin gene have been identified in more than two-thirds of Duchenne and Becker muscular dystrophy patients, the molecular mechanisms that lead to the generation of these deletions are largely unknown. Here, Alu and LINE-1 (L1) repetitive elements were shown to be present at one or other of the two ends, respectively, of a 430-kb deletion in the dystrophin gene. The breakpoint of the deletion, which stretches from exons 2 to 7, was defined more precisely by polymerase chain reaction (PCR) walking on introns 1 and 7. Finally, the region containing the breakpoint was amplified as a fragment of more than 10 kb. Sequencing of the deletion endpoint revealed the presence of an Alu sequence in intron 1, 25 kb downstream from the 3Ј end of exon 1 that was joined directly to an L1 sequence in intron 7, 4.5 kb downstream from the 3Ј end of exon 7. The deletion was calculated to be 430 kb. To our knowledge, this is a novel recombination event joining non-homologous Alu and L1 repeats, and is the largest known intrachromosomal deletion that is thought to involve repetitive genetic elements. Sequence characteristics around the breakpoint are discussed.

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Section: Introductionmentioning

confidence: 99%

Non-homologous recombination between Alu and LINE-1 repeats caused a 430-kb deletion in the dystrophin gene: a novel source of genomic instability

et al. 2000

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“…The gp91 phox gene encodes an essential component of the oxidase, and mutations including a deletion (2,3) of the gene result in X-linked chronic granulomatous disease characterized by severe and recurrent infections due to lack of superoxide generation (4). The gp91 phox gene is expressed almost uniquely in differentiated myeloid cells (5).…”

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Cooperation of STAT-1 and IRF-1 in Interferon-γ-induced Transcription of the gp91 Gene

Kumatori

Yang

Suzuki

et al. 2002

Journal of Biological Chemistry

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Interferon (IFN)-␥ induces the expression of the gp91phox gene both during myeloid differentiation and also in mature phagocytes through several cis-elements and their binding proteins. To find new cis-elements for this induction, transient expression assays were performed using a reporter gene driven by serially truncated gp91 phox promoters in U937 cells. The results suggest that a critical cis-element for induction exists in the region from bp ؊115 to ؊96 of the promoter. Site-directed mutagenesis showed that a ␥-activated sequence (GAS) element at bp ؊100 (؊100GAS) of the gp91 phox promoter plays a pivotal role for the IFN-␥-dependent activity of the bp ؊115 to ؉12 region of the gp91 phox promoter. Electrophoretic mobility shift assays using several GAS competitors and specific antibodies indicated that phosphorylated STAT-1␣ specifically binds to the ؊100GAS. Site-directed mutagenesis showed that an interferon-stimulated response element (ISRE) at bp ؊88 (؊88ISRE) mediates the induction of the gene by IFN-␥ in cooperation with ؊100GAS. Electrophoretic mobility shift assay showed that IRF-1 dominantly binds to ؊88ISRE in an IFN-␥-dependent fashion. These results demonstrate a new mechanism for IFN-␥-induced transcription of the gp91 phox gene by the cooperation of STAT-1␣ and IRF-1 binding to ؊100GAS and ؊88ISRE, respectively.

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“…Several transcription factors regulate gp91 phox gene expression through cis-elements in a 450-base pair (bp) 1 sequence in the 5Ј-flanking region of the gene. A CCAAT displacement protein (CDP/cut) (6,7) suppresses the expression of the gp91 phox gene by binding to four sites at bp Ϫ350, Ϫ220, Ϫ150, and Ϫ110 of the gene in immature myeloid cell lines.…”

mentioning

confidence: 99%

“…Mutations in the gp91 phox gene such as deletions (1) and substitutions (2) result in X-linked chronic granulomatous disease, which is characterized by severe recurrent infections due to the lack of superoxide generation (3). The gp91 phox gene is expressed in terminally differentiated phagocytes and B-lymphocytes (4,5), indicating the expression of the gene to be both lineage-and differentiation stage-specific.…”

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confidence: 99%

Eosinophil-specific Regulation of gp91 Gene Expression by Transcription Factors GATA-1 and GATA-2

Yang

Suzuki

et al. 2000

Journal of Biological Chemistry

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The glycoprotein gp91phox is an essential component of the phagocyte NADPH oxidase and is expressed in eosinophils, neutrophils, monocytes, and B-lymphocytes. We previously suggested an eosinophil-specific mechanism of gp91 phox gene expression. To elucidate the mechanism, we performed functional assays on deletion mutants of the gp91 phox promoter in various types of gp91 phox -expressing cells. A 10-base pair (bp) region from bp ؊105 to ؊96 of the promoter activated transcription of the gene in eosinophilic cells, but not in neutrophilic, monocytic, or B-lymphocytic cells. A 2-bp mutation introduced into the GATA site spanning bp ؊101 to ؊96 (؊98GATA site) of the fragment abolished its activity. Gel shift assays using a GATA competitor and specific antibodies demonstrated that both GATA-1 and GATA-2 specifically bound to the ؊98GATA site with similar affinities. Individual transfection of GATA-1 and GATA-2 into Jurkat cells, which have neither endogenous GATA-1 nor GATA-2, activated the ؊105/؉12 construct in a ؊98GATA site-dependent manner. Combined transfection of GATA-1 and GATA-2 activated the promoter less than transfection of GATA-1 alone. These results suggest that GATA-1 is an activator and that GATA-2 is a relative competitive inhibitor of GATA-1 in the expression of the gp91 phox gene in human eosinophils.

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Nonhomologous Recombination between the Cytochrome b558Heavy Chain Gene (CYBB) and LINE-1 Causes an X-Linked Chronic Granulomatous Disease

Cited by 30 publications

References 35 publications

Non-homologous recombination between Alu and LINE-1 repeats caused a 430-kb deletion in the dystrophin gene: a novel source of genomic instability

Non-homologous recombination between Alu and LINE-1 repeats caused a 430-kb deletion in the dystrophin gene: a novel source of genomic instability

Cooperation of STAT-1 and IRF-1 in Interferon-γ-induced Transcription of the gp91 Gene

Eosinophil-specific Regulation of gp91 Gene Expression by Transcription Factors GATA-1 and GATA-2

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