Just when you think you’ve got them all down, another one pops up. Among the newest ’omes to appear, please welcome the cistrome, or the global study of cis-acting trans-factors across the genome. The term, coined in November 2006 by Myles Brown at the Dana Farber Cancer Institute, came out of a groundbreaking study he led to map the entire cistrome of the estrogen receptor. His team found that this cis-acting trans-factor regulates its target genes at great distances from promoters; apparently, cis-regulatory regions distinct from promoters play a significant role in communicating which genes are turned on and off in breast cancer. The cistrome includes all of these regulatory regions.
Because the transcriptome, or the catalog of all mRNA transcripts in a cell, is highly regulated by transcription factors, new techniques have emerged to determine where transcription factor binding sites exist. Among them is ChIP-on-chip, or chromatin immunoprecipitation (ChIP) combined with microarrays, which is being used to localize transcription factor binding sites and to visualize expression changes of the genes they regulate on a genome-wide scale. The conventional approach has been to assume that most transcription factors bind promoter regions, or areas close to the genes that they regulate; Brown, however, proved that a widely distributed array of regulatory regions can influence the transcriptomic profiles of cancer.
At the American Association for Cancer Research annual meeting this spring, cistromes made their debut as the topic of a session co-chaired by Tim Huang, an associate professor at Ohio State University Medical Center who studies epigenetic changes linked to tumorigenesis. ChIP-on-chip technology allows scientists to examine the mechanism of cancer, specifically at altered binding of transcription factors in the disease state versus normal. ChIP-on-chip analysis of cistromes looks globally at transcription factor binding sites to see if or what “leads to alteration of transcription factor binding and identify whether [they’re] a sequence that one can predict,” Huang says. One can then “see which target genes are going to be activated or deactivated upon signaling stimulation and upon a transcription factor binding.”
He adds that using both whole-genome tiling arrays to map the epigenetic alterations in cancer combined with genome-wide cistrome mapping could gain even further insight into the mechanistic action of transcriptional silencing in cancer.