title: A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster.
abstract: 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 noncoding 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 retinoic acid (RA)-driven granulocytic differentiation is through RA receptor and may depend on the expression of myeloid cell development factors targeted by RA signaling. Knockdown of HOTAIRM1 quantitatively blunted RA-induced expression of HOXA1 and HOXA4 during the myeloid differentiation of NB4 cells, and selectively attenuated induction of transcripts for 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.
authors.affiliation: Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lian
authors.forename: Carolyn
authors.initials: C
authors.lastname: Padden
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
authors.forename: Joel
authors.initials: J
authors.lastname: Rozowsky
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Gingeras
authors.forename: Philipp
authors.initials: P
authors.lastname: Kapranov
authors.forename: Sherman M
authors.initials: SM
authors.lastname: Weissman
authors.forename: Peter E
authors.initials: PE
authors.lastname: Newburger
mesh_terms: D002478:Cells, Cultured; D021901:DNA, Intergenic / Q000235:genetics; D020869:Gene Expression Profiling; D018922:HL-60 Cells; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D038042:Myelopoiesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012319:RNA Polymerase II / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000099261:Homeobox A1 Protein
chemical_list: D021901:DNA, Intergenic; D018398:Homeodomain Proteins; D035683:MicroRNAs; D012319:RNA Polymerase II; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D014157:Transcription Factors; D000099261:Homeobox A1 Protein; C520321:HOXA2 protein, human; C000609546:long non-coding RNA HOTAIRM1, human; C088144:HoxA protein