In unsteady stock markets these days, who couldn’t use a hot tip to rev up their investments? Apparently, some HOXA genes also need a HOTTIP just as much as any Wall St. insider to help jump-start production. A recent Nature paper from talented teams at Stanford University and UCSF reveals that a long intergenic non-coding RNA (lincRNA) called “HOTTIP” maintains active chromatin to coordinate homeotic gene expression.
The HOXA locus encodes a cluster of homeodomain transcription factors involved in positional identity. The researchers observed two lincRNA loci at the 5’ and 3’ edges of a HOXA gene cluster: at the 3’ end, HOTAIRM1, which was identified previously as a myelopoiesis-associated lincRNA; and at the 5’ end, HOTTIP1, a newly identified lincRNA. HOTTIP1 exhibited bivalent H3K4me3 and H3K27me3 histone modifications, a pattern associated with poised regulatory sequences. The investigators observed some interesting interactions between HOTTIP RNA and HOXA genes in cells with active HOXA expression:
- Chromosomal looping brings newly transcribed HOTTIP lincRNA close to 5’ HOXA genes
- HOTTIP lincRNA binds to WDR5-MLL protein complexes, which methylate histone H3K4 to activate genes
- HOTTIP RNA targets WDR5-MLL to the 5’ HOXA locus to activate transcription
Although most lincRNAs have been implicated in gene silencing, this study demonstrates that some lincRNAs, such as HOTTIP, may function as activators of gene transcription.
So go get some hot tips for your next journal club at Nature, March 2011.