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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2526-2534.
Prepublished online as a Blood First Edition Paper on January 14, 2009; DOI 10.1182/blood-2008-06-162164.
Previous Article | Next Article 
Submitted June 10, 2008
Accepted December 29, 2008
A myelopoiesis-associated regulatory intergenic
non-coding RNA transcript within the human HOXA cluster
Xueqing Zhang, Zheng Lian, Carolyn Padden, Mark B. Gerstein, Joel Rozowsky, Michael Snyder, Thomas R. Gingeras, Philipp Kapranov, Sherman M. Weissman, and Peter E. Newburger*
Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA, United States
Department of Genetics, Yale University, New Haven, CT, United States
Department of Molecular Biochemistry and Biophysics, Yale University, New Haven, CT, United States
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, United States
Affymetrix, Inc., Santa Clara, CA, United States
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA, United States
* Corresponding author; email: peter.newburger{at}umassmed.edu.
We have identified an intergenic transcriptional activity that is located between the human HOXA1 and HOXA2 genes, shows myeloid-specific expression, and is up-regulated during granulocytic differentiation. The novel gene, termed HOTAIRM1 (HOX Antisense Intergenic RNA Myeloid 1), is transcribed antisense to the HOXA genes and originates from the same CpG island that embeds the start site of HOXA1. The transcript appears to be a non-coding RNA containing no long open-reading frame, sucrose gradient analysis shows no association with polyribosomal fractions. HOTAIRM1 is the most prominent intergenic transcript expressed and up-regulated during induced granulocytic differentiation of NB4 promyelocytic leukemia and normal human hematopoietic cells; its expression is specific to the myeloid lineage. Its induction during retinoid acid (RA)-driven granulocytic differentiation is through RA receptor and may depend on the expression of myeloid cell development factors targeted by RA signaling. Knock-down of HOTAIRM1 quantitatively blunted RA-induced expression of HOXA1 and HOXA4 during the myeloid differentiation of NB4 cells, and selectively attenuated induction of the myeloid differentiation genes CD11b and CD18, but did not noticeably impact the more distal HOXA genes. These findings suggest that HOTAIRM1 plays a role in the myelopoiesis through modulation of gene expression in the HOXA cluster.

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