Protein reverses engineering of chromosome structure

An enzyme, a histone demethylase, removes methyl groups appended to histones, nuclear proteins that organize DNA and regulate gene activity. Methyl groups and other chemical tags on histones regulate how the DNA wraps around the proteins to form a chromatin structure that either promotes gene activity or represses it. Chromatin, which contains DNA, RNA, and various proteins, is the substance that constitutes chromosomes. Professor Yang Shi and his colleagues discovered the demethylase during functional studies of novel gene repressor proteins. The enzyme, dubbed LSD1 for lysine specific demethylase 1, turns off gene activity by removing one particular methyl tag that normally functions as a green light for gene activity. Cells engineered to lack LSD1 accumulated methylated histones and turned on genes that were previously silent. In some tumors, addition of methyl groups at LSD1’s target lysine seems to play a role in aberrant activation of genes that drive cell growth, suggesting that LSD1 might be useful to counteract this progrowth signal. “Previously, people thought that histone methylation was stable and irreversible,” said Shi. “The fact that we’ve identified a demethylase suggests a more dynamic process of gene regulation via methylation of histones. The idea of yin and yang is universal in biology; our results show that histone methylation is no different.”