The Super-Enhancer-Derived alncRNA-EC7/Bloodlinc Potentiates Red Blood Cell Development in trans
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Author(s)
Knoll, Marko
Alvarez, Juan Rene
Gromatzky, Austin A.
Lodish, Harvey F
Date Issued
June 2017
Journal
Cell Reports
Publisher
Elsevier
Citation
Alvarez-Dominguez, Juan R. et al. “The Super-Enhancer-Derived alncRNA-EC7/Bloodlinc Potentiates Red Blood Cell Development in Trans.” Cell Reports 19, 12 (June 2017): 2503–2514 © 2017 The Author(s)
Version
Final published version
Abstract
Enhancer-derived RNAs are thought to act locally by contributing to their parent enhancer function. Whether large domains of clustered enhancers (super-enhancers) also produce cis-acting RNAs, however, remains unclear. Unlike typical enhancers, super-enhancers form large spans of robustly transcribed chromatin, amassing capped and polyadenylated RNAs that are sufficiently abundant to sustain trans functions. Here, we show that one such RNA, alncRNA-EC7/Bloodlinc, is transcribed from a super-enhancer of the erythroid membrane transporter SLC4A1/BAND3 but diffuses beyond this site. Bloodlinc localizes to trans-chromosomal loci encoding critical regulators and effectors of terminal erythropoiesis and directly binds chromatin-organizing and transcription factors, including the chromatin attachment factor HNRNPU. Inhibiting Bloodlinc or Hnrnpu compromises the terminal erythropoiesis gene program, blocking red cell production, whereas expressing Bloodlinc ectopically stimulates this program and can promote erythroblast proliferation and enucleation in the absence of differentiation stimuli. Thus, Bloodlinc is a trans-acting super-enhancer RNA that potentiates red blood cell development. Keywords
enhancer RNA; super-enhancer; long non-coding RNA; erythropoiesis;
red blood cell
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
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Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI of Published Version
https://doi.org/10.1016/J.CELREP.2017.05.082
