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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F13%3A33144967" target="_blank" >RIV/61989592:15110/13:33144967 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00098892:_____/13:#0000525

Výsledek na webu

<a href="http://onlinelibrary.wiley.com/doi/10.1002/humu.22383/full" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1002/humu.22383/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/humu.22383" target="_blank" >10.1002/humu.22383</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 r

Název v anglickém jazyce

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

Popis výsledku anglicky

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 r

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2013

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Human Mutation

ISSN

1059-7794

e-ISSN

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Svazek periodika

34

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

5

Strana od-do

1361-1365

Kód UT WoS článku

000324752700008

EID výsledku v databázi Scopus

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