title: Structural and functional differences in the long non-coding RNA hotair in mouse and human.
abstract: Long non-coding RNAs regulate various biological processes such as dosage compensation, imprinting, and chromatin organization. HOTAIR, a paradigm of this new class of RNAs, is localized within the human HOXC gene cluster and was shown, in human cells, to regulate HOXD genes in trans via the recruitment of Polycomb Repressive Complex 2 (PRC2), followed by the trimethylation of lysine 27 of histone H3. We looked for the presence of Hotair in mice to assess whether this in trans mechanism was conserved, in particular at the developmental stages, when Hoxd genes must be tightly regulated. We show that the cognate mouse Hotair is poorly conserved in sequence; and its absence, along with the deletion of the HoxC cluster, has surprisingly little effect in vivo, neither on the expression pattern or transcription efficiency, nor on the amount of K27me3 coverage of different Hoxd target genes. We conclude that Hotair may have rapidly evolved within mammals and acquired a functional importance in humans that is not easily revealed in mice. Alternatively, redundant or compensatory mechanisms may mask its function when studied under physiological conditions.
authors.affiliation: School of Life Sciences, Federal Institute of Technology, Lausanne, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schorderet
authors.forename: Denis
authors.initials: D
authors.lastname: Duboule
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017124:Conserved Sequence; D005091:Exons; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D051379:Mice; D005810:Multigene Family; D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015533:Transcriptional Activation
chemical_list: C000608169:HOTAIR long non-coding RNA, mouse; C484731:HOXC11 protein, human; D018398:Homeodomain Proteins; C111583:Hoxc11 protein, mouse; C469340:Hoxc12 protein, mouse; D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins