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A long non-coding RNA promotes full activation of adult gene expression in the chicken ?-globin domain.

ABSTRACT: Long non-coding RNAs (lncRNAs) were recently shown to regulate chromatin remodelling activities. Their function in regulating gene expression switching during specific developmental stages is poorly understood. Here we describe a nuclear, non-coding transcript responsive for the stage-specific activation of the chicken adult ?(D) globin gene. This non-coding transcript, named ?-globin transcript long non-coding RNA (lncRNA-?GT) is transcriptionally upregulated in late stages of chicken development, when active chromatin marks the adult ?(D) gene promoter. Accordingly, the lncRNA-?GT promoter drives erythroid-specific transcription. Furthermore, loss of function experiments showed that lncRNA-?GT is required for full activation of the ?(D) adult gene and maintenance of transcriptionally active chromatin. These findings uncovered lncRNA-?GT as an important part of the switching from embryonic to adult ?-globin gene expression, and suggest a function of lncRNA-?GT in contributing to the maintenance of adult ?-globin gene expression by promoting an active chromatin structure.

SUBMITTER: Arriaga-Canon C

PROVIDER: S-EPMC3928180 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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A long non-coding RNA promotes full activation of adult gene expression in the chicken α-globin domain.

Arriaga-Canon Cristian C Fonseca-Guzmán Yael Y Valdes-Quezada Christian C Arzate-Mejía Rodrigo R Guerrero Georgina G Recillas-Targa Félix F

Epigenetics 20131106 1

Long non-coding RNAs (lncRNAs) were recently shown to regulate chromatin remodelling activities. Their function in regulating gene expression switching during specific developmental stages is poorly understood. Here we describe a nuclear, non-coding transcript responsive for the stage-specific activation of the chicken adult α(D) globin gene. This non-coding transcript, named α-globin transcript long non-coding RNA (lncRNA-αGT) is transcriptionally upregulated in late stages of chicken developme ...[more]

PMID: 24196393

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Project description:UNLABELLED: BACKGROUND: The ?-globin gene domains of vertebrate animals constitute popular models for studying the regulation of eukaryotic gene transcription. It has previously been shown that in the mouse the developmental switching of globin gene expression correlates with the reconfiguration of an active chromatin hub (ACH), a complex of promoters of transcribed genes with distant regulatory elements. Although it is likely that observations made in the mouse ?-globin gene domain are also relevant for this locus in other species, the validity of this supposition still lacks direct experimental evidence. Here, we have studied the spatial organization of the chicken ?-globin gene domain. This domain is of particular interest because it represents the perfect example of the so-called 'strong' tissue-specific gene domain flanked by insulators, which delimit the area of preferential sensitivity to DNase I in erythroid cells. RESULTS: Using chromosome conformation capture (3C), we have compared the spatial configuration of the ?-globin gene domain in chicken red blood cells (RBCs) expressing embryonic (3-day-old RBCs) and adult (9-day-old RBCs) ?-globin genes. In contrast to observations made in the mouse model, we found that in the chicken, the early embryonic ?-globin gene, ?, did not interact with the locus control region in RBCs of embryonic lineage (3-day RBCs), where this gene is actively transcribed. In contrast to the mouse model, a strong interaction of the promoter of another embryonic ?-globin gene, ?, with the promoter of the adult ?-globin gene, ?A, was observed in RBCs from both 3-day and 9-day chicken embryos. Finally, we have demonstrated that insulators flanking the chicken ?-globin gene domain from the upstream and from the downstream interact with each other, which places the area characterized by lineage-specific sensitivity to DNase I in a separate chromatin loop. CONCLUSIONS: Taken together, our results strongly support the ACH model but show that within a domain of tissue-specific genes, the active status of a promoter does not necessarily correlate with the recruitment of this promoter to the ACH.

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A long non-coding RNA promotes full activation of adult gene expression in the chicken ?-globin domain.

Publications

A long non-coding RNA promotes full activation of adult gene expression in the chicken α-globin domain.

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