Unravelling the essentials of the Y chromosome

Researchers have found that an enzyme that regulates the expression of the Y-chromosome gene Sry plays a pivotal role in mammalian sex determination.

Expression of the Sry gene is required for male development - the timing and amount of expression of the Sry transcription factor is critical for triggering the testis-determining pathway.

University of Queensland and Japanese scientists have shown that mice lacking the Jmjd1a enzyme develop as females despite having a Y chromosome.

Professor Peter Koopman, from UQ’s Institute for Molecular Bioscience, said the discovery provided new information on the earliest steps the body takes in becoming male or female.

“Most mammals, including humans and mice, are programmed to develop as females unless a specific Y-chromosome gene called Sry is present to trigger male development during embryonic life,” Koopman said.

“We knew that Sry is responsible for switching on maleness genes, but what we didn’t know is that the DNA containing Sry needs be unwound before the gene can become active.”

The researchers found that the histone demethylating enzyme Jmjd1a regulates the expression of the Sry gene. Histone proteins create a spindle around which DNA winds, enabling it to be packaged or organised into chromosomes.

“It’s as if the DNA is a ball of string that needs to be unravelled by Jmjd1a to expose the Sry gene before it can be used,” said Koopman.

“This latest discovery has put the spotlight on DNA packaging as a major determinant of the sex of the embryo.”

“In broader terms it continues to open our eyes to the enormous amount of activity occurring in every cell to coordinate when and where each of our 30,000 genes is active - it’s a huge logistical task.”

Koopman, who was part of the team that originally discovered the Sry gene, said the work could also help with understanding intersex conditions where people are not biologically male or female but can have characteristics of both.

The study was published in the journal Science.