Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation

Juan R. Alvarez-Dominguez, Wengian Hu, Bingbing Yuan, Jiahai Shi, Staphany S. Park, Austin A. Gromatzky, Alexander Van Oudenaarden, Harvey F. Lodish

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Erythropoiesis is regulated atmultiple levels to ensure the proper generation ofmature red cells undermultiple physiological conditions. To probe the contribution of long noncoding RNAs (lncRNAs) to this process, we examined >1 billion RNA-seq reads of polyadenylated and nonpolyadenylated RNA from differentiating mouse fetal liver red blood cells and identified 655 lncRNA genes including not only intergenic, antisense, and intronic but also pseudogene and enhancer loci. More than 100 of these genes are previously unrecognized and highly erythroid specific. By integrating genome-wide surveys of chromatin states, transcription factor occupancy, and tissue expression patterns, we identify multiple lncRNAs that are dynamically expressed during erythropoiesis, show epigenetic regulation, and are targeted by key erythroid transcription factors GATA1, TAL1, or KLF1. We focus on 12 such candidates and find that they are nuclear-localized and exhibit complex developmental expression patterns. Depleting them severely impaired erythrocyte maturation, inhibiting cell size reduction and subsequent enucleation. One of them, alncRNA-EC7, is transcribed from an enhancer and is specifically needed for activation of the neighboring gene encoding BAND 3. Our study provides an annotated catalog of erythroid lncRNAs, readily available through an online resource, and shows that diverse types of lncRNAs participate in the regulatory circuitry underlying erythropoiesis.

Original languageEnglish (US)
Pages (from-to)570-581
Number of pages12
JournalBlood
Volume123
Issue number4
DOIs
StatePublished - Jan 23 2014
Externally publishedYes

Fingerprint

Long Noncoding RNA
Cells
Erythropoiesis
Genes
GATA1 Transcription Factor
Erythrocytes
Pseudogenes
Gene encoding
Cell Size
Epigenomics
Liver
Transcriptional Activation
Chromatin
Blood
Transcription Factors
Chemical activation
Genome
RNA
Tissue
Messenger RNA

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Alvarez-Dominguez, J. R., Hu, W., Yuan, B., Shi, J., Park, S. S., Gromatzky, A. A., ... Lodish, H. F. (2014). Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation. Blood, 123(4), 570-581. https://doi.org/10.1182/blood-2013-10-530683

Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation. / Alvarez-Dominguez, Juan R.; Hu, Wengian; Yuan, Bingbing; Shi, Jiahai; Park, Staphany S.; Gromatzky, Austin A.; Van Oudenaarden, Alexander; Lodish, Harvey F.

In: Blood, Vol. 123, No. 4, 23.01.2014, p. 570-581.

Research output: Contribution to journalArticle

Alvarez-Dominguez, JR, Hu, W, Yuan, B, Shi, J, Park, SS, Gromatzky, AA, Van Oudenaarden, A & Lodish, HF 2014, 'Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation', Blood, vol. 123, no. 4, pp. 570-581. https://doi.org/10.1182/blood-2013-10-530683
Alvarez-Dominguez, Juan R. ; Hu, Wengian ; Yuan, Bingbing ; Shi, Jiahai ; Park, Staphany S. ; Gromatzky, Austin A. ; Van Oudenaarden, Alexander ; Lodish, Harvey F. / Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation. In: Blood. 2014 ; Vol. 123, No. 4. pp. 570-581.
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