With the EpiGenie Fortune Telling Machine in the shop most of the time, it’s pretty difficult for us to predict much of anything. (Yeah, we didn’t see the whole ‘twerking’ phenomenon coming either!) But some enterprising researchers have developed a way to classify and predict the epigenetic and transcriptional activities of various promoter regions based on the GC-skew and R-loops associated with their CpG islands (CGI).
Scientists at UC Davis found that GC-skew (strand asymmetry in GC residue distribution) and R-loops (RNA:DNA hybrid structures formed by transcribed RNA looping back to hybridize with the template DNA) can tell you quite a bit more about how a promoter performs than just the sequence or DNA methylation state alone.
By using their SkewR algorithm, the team was able to identify four classes of promoters based on the GC-skew and R-loop profile.
Class I promoters:
- Strong CGI promoters
- Highest CpG density and GC composition
- Rise in positive GC skew at the TSS
- Associated with prototypical housekeeping genes
- TSS protected by DNA methylation marks
- Increased H4K20me1 and H3K79me2 deposits
Class II promoters:
- Weaker CGIs characterized by shorter lengths
- Reduced CpG density and GC composition
- Sharply reduced shift in GC skew at the TSS
- Associated with genes involved in housekeeping, mitochondrial function, organelle biology, and ZNF type transcription factors
- Much lower transcriptional output than Class I loci
- TSS protected by DNA methylation marks
- Increased H4K20me1 and H3K79me2 deposits
Class III promoters:
- CpG-poor loci with weak GC skew
- Enriched at genes with tissue-specific functions
Class IV promoters:
- Strong GC skew in the ‘‘reverse’’ orientation (compared to Class I promoters) Displayed CpG densities, GC percentages, and lengths similar to Class I promoters, but with clear negative GC skew upstream of the TSS
- Associated with genes related to transcriptional regulation, morphogenesis, cell fate commitment, and transcription factors
- TSS protected by DNA methylation
- Enriched with H3K27me3 marks
As a package these newly defined promoter classes can be used to associate distinct gene ontologies and epigenetic signatures based on their GC skew and R-loop charcteristics.
Take a deeper look at what your favorite promoter might do in Genome Research October 2013