Journal
BLOOD
Volume 132, Issue 18, Pages 1963-1973Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2018-07-862003
Keywords
-
Categories
Funding
- Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [DK075033]
Ask authors/readers for more resources
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 (A)gamma-globin (HBG1). BGLT3 and gamma-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 gamma-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 gamma-globin genes and BGLT3 sequences. In contrast, the BGLT3 transcript is dispensable for gamma-globin/BGLT3 looping but interacts with the mediator complex on chromatin. Manipulation of the BGLT3 locus does not compromise g-globin gene long-range looping interactionswith the gamma-globin locus control region (LCR). These data reveal that BGLT3 regulates gamma-globin transcription in a developmental stage-specific fashion together with the LCR by serving as a separate means to increase RNA Pol II density at the gamma-globin promoters.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available