Fetal γ-globin genes are regulated by the BGLT3 long noncoding RNA locus.

Blood
Maria Soledad IvaldiAnn Dean

Abstract

Long noncoding RNAs (lncRNAs) are increasingly being appreciated as participants in regulation of important cellular processes, including transcription. Because lncRNAs are highly cell type specific, they have the potential to contribute to the unique transcriptional repertoire of diverse cells, but underlying mechanisms are unclear. We studied BGLT3, an erythroid lncRNA encoded downstream of Aγ-globin (HBG1). BGLT3 and γ-globin genes are dynamically cotranscribed in erythroid cells in vivo. Deletion of BGLT3 using CRISPR/Cas9 editing shows that it specifically contributes to regulation of γ-globin genes. We used reduction or overexpression of the RNA and inhibition of transcription through the locus by CRISPRi to distinguish functions of the transcript vs the underlying sequence. Transcription of the BGLT3 locus is critical for looping between the γ-globin genes and BGLT3 sequences. In contrast, the BGLT3 transcript is dispensable for γ-globin/BGLT3 looping but interacts with the mediator complex on chromatin. Manipulation of the BGLT3 locus does not compromise γ-globin gene long-range looping interactions with the β-globin locus control region (LCR). These data reveal that BGLT3 regulates γ-globin transcription in a developme...Continue Reading

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Nov 6, 2018·Blood·Gerd A Blobel, Merlin Crossley
Dec 4, 2019·Transcription·Michael W LewisHector L Franco
Jun 10, 2020·Nature Structural & Molecular Biology·Vittorio Sartorelli, Shannon M Lauberth
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Jul 20, 2021·Current Opinion in Structural Biology·Juhyun Kim, Ann Dean
Aug 19, 2021·Nature Communications·Yong ShenVijay G Sankaran

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