| Summary: | <p>Abstract</p> <p>Background</p> <p>Thousands of different long non-coding RNAs are expressed during embryonic development, but the function of these molecules remains largely unexplored.</p> <p>Results</p> <p>Here we characterize the expression and function of <it>Six3OS</it>, 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 <it>Six3OS </it>reveals that it plays an essential role in regulating retinal cell specification. We further observe that <it>Six3OS </it>regulates Six3 activity in developing retina, but does not do so by modulating Six3 expression. Finally, we show that <it>Six3OS </it>binds directly to Ezh2 and Eya family members, indicating that <it>Six3OS </it>can act as a molecular scaffold to recruit histone modification enzymes to Six3 target genes.</p> <p>Conclusions</p> <p>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.</p>
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