Using a new methodology called Global Run-On Sequencing (GRO-seq), developed by collaborators at Cornell University, the researchers were able to observe in a very short period of time how estrogen regulates the growth of cells on a molecular level. In previous studies, researchers had to make inferences about gene transcription - the process of creating an RNA copy of a DNA sequence - based on steady state gene expression patterns, or static images that are captured over hours and days. Instead, GRO-seq provides a zoomed-in view of genome-wide transcription as it's happening, a virtual "map" of the position and orientation of all engaged RNA polymerases at high resolution.

"We now have a method in which we can look at what estrogen is doing as soon as it enters the cell," said Dr. Kraus, who also serves as vice chairman for basic science for obstetrics and gynecology. "The results were really surprising. The genes get turned on and off in a very short time scale."

In mapping the transcriptome - all the genes that are transcribed in a cell at any one time - Dr. Kraus and his collaborators discovered that short treatments with estrogen regulate one-fourth of all the different types of RNAs produced in the breast cancer cell type.

"This is a profound effect on the genome and something that had never been detected before. It's essentially changing a quarter of the transcripts that are produced in the cell," said Dr. Kraus, who left Cornell last summer to join the UT Southwestern faculty.

"You can really see the logic of this mitogenic response," he said. "It's not just about estrogen stimulating the production of some protein-coding genes. It's about estrogen coordinating transcriptional responses across the genome that allows it to produce this effect."

Source: UT Southwestern Medical Center