A team of researchers led by Baylor College of Medicine found that not only do individual mammalian cells in a population fail to respond synchronously to estrogen stimulation, but neither do individual gene copies, known as alleles. The findings, published in the recent edition of the journal Nucleic Acids Research, also showed that neither the level of estrogen receptor nor its activation status determined asynchronous cellular responses.
However, a small molecule inhibitor of selected estrogen coregulators increased the response of individual alleles to hormone, establishing a previously unrecognized mode of regulation of estrogen-induced gene activation at the single cell level.
“Estrogen is a type of steroid hormone that modulates a large number of biological functions, both in males and females, by regulating the activity of hundreds of genes per cell,” said first author Dr. Fabio Stossi, associate professor of molecular and cellular biology and technical director of the Integrated Microscopy Core at Baylor.
A great deal is known about how estrogen triggers its effects. It binds to a nuclear transcription factor (estrogen receptor, or ER), which in turn interacts with specific DNA sequences facilitating the recruitment of coregulators that participate in the regulation of gene expression. It was assumed that this process would likely happen simultaneously in all the ER-containing cells in a population that was stimulated with estrogen. However, little was known of how actual single cells or individual copies of the same gene responded, which is why researchers did not anticipate these finding at the single cell level.