Last February, a team of standouts from the publication factory in Boston (aka Broad Institute), published work highlighting over 1,500 previously un-annotated genomic sequences that housed large intervening non-coding RNAs known as lincRNAs. These transcripts showed similar expression patterns as mRNA and they exhibited more conservation than neutral sequences, indicating they were probably functional, but the team was left with more questions than answers.
Well the Broad group struck again last week, proving that sequels can live up to the original. Using the same chromatin signature (K4-K36 domain) that they used to discover lincRNAs, they took a closer look at six human cell types and identified more novel transcripts, upping the number of lincRNAs to 3,289.
Since there are a few examples of larger ncRNAs that bind chromatin modifying proteins, the team wanted to see if these lincRNAs were also in cahoots with chromatin modifying proteins. A few RNA coimmunoprecipitation (RIP) Chip and siRNA transfections later, the team found that:
- Almost 40% of the lincRNAs were hanging out in close proximity to chromatin modifying proteins like PRC2 and CoREST.
- Knocking out lincRNAs that were associated with PRC2 led to reactivation of genes normally silenced by PRC2
Whether or not the lincRNAs are directly guiding chromatin modifying complexes to specific loci and how they pull this off remains to be answered, so you’ll have to stay tuned.
Until then, you can get all the details of this gem online later today or tomorrow at PNAS, June 2009.