GeneID: 451

Description:
BGLT3 is an erythroid-specific long non-coding RNA (lncRNA) implicated in the regulation of γ-globin gene expression. The transcription of BGLT3 is consistently associated with γ-globin transcription in erythroid cells. Deletion of BGLT3 using CRISPR/Cas9 editing shows that it specifically contributes to regulation of γ-globin genes. Experiments showed that the BGLT3 region is occupied by the NLI/Ldb1 core complex, indicating that γ-globin transcription or silencing is mediated through long-range LCR interactions that involved looping from the BGLT3 sequences to the γ-globin genes. The BGLT3 region is also occupied by the transcriptional repressor ETO2 (via NL1/Ldb1 complex) and the γ-globin repressor BCL11A. In high-HbF cells (mainly γ-globin expression), BGLT3 transcription is upregulated and the participation of the ETO2 in the NLI/Ldb1 complex and BCL11A occupancy at BGLT3 in reduced. BGLT3 can regulate γ-globin transcripion via multiple mechanisms, including maintaining an enhancer-like state, looping to the γ-globin genes and recruiting coregulators, possibly through the BGLT3 transcript itself. Sequence variation associated with γ-globin levels in sickle cell patients and a sample of carriers of β-thalassaemia mutations.

Synonyms: N/A

Comments:
N/A

1. Kiefer CM, Lee J, Hou C, Dale RK, Lee YT, Meier ER, Miller JL, Dean A, Distinct Ldb1/NLI complexes orchestrate γ-globin repression and reactivation through ETO2 in human adult erythroid cells., Blood, 118(23), 6200-8, 2011
2. Blobel GA, Crossley M, Charting a noncoding gene for γ-globin activation., Blood, 132(18), 1865-1867, 2018
3. Ivaldi MS, Diaz LF, Chakalova L, Lee J, Krivega I, Dean A, Fetal γ-globin genes are regulated by the long noncoding RNA locus., Blood, 132(18), 1963-1973, 2018