Priming genes for future activation

Unlike less versatile muscle or nerve cells, embryonic stem cells are equipped to assume any cellular role. Scientists call this “pluripotency,” meaning that as an organism develops, stem cells must be ready at a moment’s notice to activate highly diverse gene expression programs that will turn them into blood, brain, or kidney cells.

Scientists from the lab of Investigator Ali Shilatifard, PhD, revealed that one way cells stay so plastic is by stationing a protein called Ell3 at stretches of DNA required to activate a neighboring gene, genomic regions known as enhancers.

A few years back, Chengqi Lin, a curious Open University graduate student working in the Shilatifard lab, had started exploring a potential function for the previously neglected gene by initiating a global search for regions occupied by Ell3 in the genome of mouse embryonic stem cells. Lin collaborated with Alexander Garruss, a bioinformatician in Shilatifard’s lab, and their work revealed that Ell3 sits on more than 5,000 enhancers, including many that regulate genes governing stem cell maturation into spinal cord, kidney, and blood cells. This finding is significant as many of these same genes are abnormally switched on in cancer.

In a surprising coda to the study, the team discovered that Ell3 and Pol II were present in mouse sperm nuclei. In mammals, gene expression regulated by Pol II, a process known as transcription, does not begin until the formation of a single-celled zygote, that is, well after the union of sperm and egg germ cells. “The presence of Ell3 in sperm suggests that it may serve as an epigenetic marker by bookmarking inactive gene enhancers for future activation in the embryo.”

The study was published in the December 27, 2012, online issue of Cell.