While ‘Dark Matter’ is thought to constitute roughly 85% of the cosmos, our genomic dark matter (i.e. noncoding RNAs) makes up an even larger portion (~95%) of our genetic content. Leaving the vastness of outer space to astrophysicists, Dr. Bryan Venters and Dr. Franklin Pugh at Pennsylvania State University focused on creating a map of the genomic organization for all of the RNA transcription initiation sites that shape our ‘inner space’.

For Dr. Venters, the most interesting aspect of the research was “the level of mechanistic detail we were able to observe at the core promoter on a genomic scale.” In their research they deployed a technique known as “ChIP-exo” (chromatin immunoprecipitation followed by lambda exonuclease digestion and sequencing), which allowed them to “spatially resolve the transition from transcription initiation to elongation in living cells by focusing on three components of the pre-initiation complex (PIC): TBP, TFIIB, and Pol II.” Here’s what they found:

“Much of the noncoding transcription in the human K562 leukemia cell line was driven by specific PICs.” This was surprising to Dr. Venters “because it was unknown whether the pervasive transcription reported recently was just biological noise arising from random Pol II collisions with chromatin or whether it was more specific in nature.”

The results “indicate that pervasive noncoding transcription is a regulated event that is similar to initiation at canonical promoters.”

Dr. Venters concludes that “the high sensitivity and near base pair resolution of ChIP-exo allowed us to identify nearly 160,000 PICs in human cells (more than any other study to date). Analysis of these PICs revealed that the human promoters are not truly TATA-less and that noncoding transcription arises from specific, regulated initiation complexes.”

Moving forward, Dr. Venters has a new faculty appointment at Vanderbilt, where his “research program is focused on understanding the transcriptional mechanisms driving cancer using functional genomic approaches.” The ChIP-exo approach will continue to be a central aspect of his efforts to “elucidate gene regulatory networks relevant to human disease.”

See where transcription is getting it’s start in Nature, September 2013