title: The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity.
abstract: BACKGROUND
  Thousands of different long non-coding RNAs are expressed during embryonic development, but the function of these molecules remains largely unexplored.
  
  
  RESULTS
  Here we characterize the expression and function of Six3OS, a long non-coding RNA that is transcribed from the distal promoter region of the gene encoding the homeodomain transcription factor Six3. Overexpression and knockdown analysis of Six3OS reveals that it plays an essential role in regulating retinal cell specification. We further observe that Six3OS regulates Six3 activity in developing retina, but does not do so by modulating Six3 expression. Finally, we show that Six3OS binds directly to Ezh2 and Eya family members, indicating that Six3OS can act as a molecular scaffold to recruit histone modification enzymes to Six3 target genes.
  
  
  CONCLUSIONS
  Our findings demonstrate a novel mechanism by which promoter-associated long non-coding RNAs can modulate the activity of their associated protein coding genes, and highlight the importance of this diverse class of molecules in the control of neural development.
authors.affiliation: Department of Neuroscience, Neurology and Ophthalmology, Center for High-Throughput Biology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Rapicavoli
authors.forename: Erin M
authors.initials: EM
authors.lastname: Poth
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.forename: Seth
authors.initials: S
authors.lastname: Blackshaw
mesh_terms: D000818:Animals; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D057809:HEK293 Cells; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D000097607:Homeobox Protein SIX3
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D022661:RNA, Untranslated; D000097607:Homeobox Protein SIX3