A new study found that estrogen hormones bind to the estrogen receptor in the cell nucleus and trigger the recruitment of coactivators in a specific order. In the study, published yesterday in Molecular Cell, a team of researchers at Baylor College of Medicine, the University of Texas MD Anderson Cancer Center, and the University of Texas Health Science Center at Houston showed that the sequential recruitment of coactivators is not simply adding molecules to the complex, it results in dynamic specific structural and functional changes that are necessary for effective regulation of gene expression.
"Experimental evidence suggests that different estrogen-receptor coactivators communicate and cooperate with each other to regulate gene expression," said corresponding author Bert O'Malley, chair and professor of molecular and cellular biology and Thomas C. Thompson Chair in Cell Biology at Baylor College of Medicine. "However, how this communication takes place and how it guides the sequence of events that regulate gene expression was not clear."
The scientists combined cryo-electron microscopy structure analysis and biochemical techniques to show how the recruitment of a specific coactivator, CARM1, into the complex guides the subsequent steps leading to gene activation.
"For the estrogen receptor complex to be able to regulate gene expression, the coactivator CARM1 needs to be added after other coactivators have been incorporated into the complex. We discovered that when CARM1 is added, it changes the complex both chemically and structurally, and these changes guide subsequent steps that lead to gene activation," said first author Ping Yi, assistant professor of molecular and cellular biology at Baylor.
The scientists now have a better and more clear understanding how estrogen regulation works and how it is playing a role in normal female sexual development, male sexual funtion, the reproductive system, and breast cancer.