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rdfs:seeAlso
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Description
| - We describe the molecular etiology of ß(+) -thalassemia that is caused by the insertion of the full-length transposable element LINE-1 (L1) into the intron-2 of the ß-globin gene (HBB). The transcript level of the affected ß-globin gene was severely reduced. The remaining transcripts consisted of full-length, correctly processed ß-globin mRNA and a minute amount of three aberrantly spliced transcripts with a decreased half-life due to activation of the nonsense-mediated decay pathway. The lower steady-state amount of mRNA produced by the ß-globinL1 allele also resulted from a reduced rate of transcription and decreased production of full-length ß-globin primary transcripts. The promoter and enhancer sequences of the ß-globinL1 allele were hypermethylated; however, treatment with a demethylating agent did not restore the impaired transcription. A histone deacetylase inhibitor partially reactivated the ß-globinL1 transcription despite permanent ß-globinL1 promoter CpG methylation. This result indicates that the decreased rate of transcription from the ß-globinL1 allele is associated with an altered chromatin structure. Therefore, the molecular defect caused by intronic L1 insertion in the ß-globin gene represents a novel etiology of ß-thalassemia.
- We describe the molecular etiology of ß(+) -thalassemia that is caused by the insertion of the full-length transposable element LINE-1 (L1) into the intron-2 of the ß-globin gene (HBB). The transcript level of the affected ß-globin gene was severely reduced. The remaining transcripts consisted of full-length, correctly processed ß-globin mRNA and a minute amount of three aberrantly spliced transcripts with a decreased half-life due to activation of the nonsense-mediated decay pathway. The lower steady-state amount of mRNA produced by the ß-globinL1 allele also resulted from a reduced rate of transcription and decreased production of full-length ß-globin primary transcripts. The promoter and enhancer sequences of the ß-globinL1 allele were hypermethylated; however, treatment with a demethylating agent did not restore the impaired transcription. A histone deacetylase inhibitor partially reactivated the ß-globinL1 transcription despite permanent ß-globinL1 promoter CpG methylation. This result indicates that the decreased rate of transcription from the ß-globinL1 allele is associated with an altered chromatin structure. Therefore, the molecular defect caused by intronic L1 insertion in the ß-globin gene represents a novel etiology of ß-thalassemia. (en)
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Title
| - ß-Thalassemia Due to Intronic LINE-1 Insertion in the ß-Globin Gene (HBB): Molecular Mechanisms Underlying Reduced Transcript Levels of the ß-GlobinL1 Allele
- ß-Thalassemia Due to Intronic LINE-1 Insertion in the ß-Globin Gene (HBB): Molecular Mechanisms Underlying Reduced Transcript Levels of the ß-GlobinL1 Allele (en)
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skos:prefLabel
| - ß-Thalassemia Due to Intronic LINE-1 Insertion in the ß-Globin Gene (HBB): Molecular Mechanisms Underlying Reduced Transcript Levels of the ß-GlobinL1 Allele
- ß-Thalassemia Due to Intronic LINE-1 Insertion in the ß-Globin Gene (HBB): Molecular Mechanisms Underlying Reduced Transcript Levels of the ß-GlobinL1 Allele (en)
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skos:notation
| - RIV/61989592:15110/13:33144967!RIV14-MZ0-15110___
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http://linked.open...avai/predkladatel
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
| - P(EE2.3.30.0041), P(NT11208), P(NT13587), S
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http://linked.open...iv/cisloPeriodika
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http://linked.open...vai/riv/dodaniDat
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http://linked.open...aciTvurceVysledku
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http://linked.open.../riv/druhVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...titaPredkladatele
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http://linked.open...dnocenehoVysledku
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http://linked.open...ai/riv/idVysledku
| - RIV/61989592:15110/13:33144967
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - ß-thalassemia; ß-globin; epigenetic repression; LINE-1; HBB (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
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http://linked.open...in/vavai/riv/obor
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http://linked.open...ichTvurcuVysledku
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http://linked.open...cetTvurcuVysledku
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http://linked.open...vavai/riv/projekt
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http://linked.open...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Indrák, Karel
- Kučerová, Jana
- Divoká, Martina
- Divoký, Vladimír
- Prchal, Josef T.
- Láníková, Lucie
- Issa, Jean-Pierre
- Papayannopoulou, Thalia
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http://linked.open...ain/vavai/riv/wos
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issn
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number of pages
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http://bibframe.org/vocab/doi
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http://localhost/t...ganizacniJednotka
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