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David Bricker

Last modified: Tuesday, June 18, 2002

IU researchers find protein may help shut off sex chromosomes in roundworms

Method of X chromosome silencing is new


BLOOMINGTON, Ind. -- A roundworm's ability to make healthy sperm and egg cells -- and therefore offspring -- depends on at least one protein that apparently helps turn off the very sex chromosomes that determine the worm's sex, say Indiana University researchers.

In this week's (June 21) issue of the journal Science, developmental biologist Susan Strome and her colleagues report that the sex or X chromosomes in the roundworm Caenorhabditis elegans lack a protein that seems to play a role in keeping genes active. The protein, called MES-4, is found in abundance on the worm's other chromosomes.

The finding reveals a new strategy for controlling the activation of X chromosome genes in animals that have different sexes and different numbers of X chromosomes, and it identifies the first such protein to be excluded from the X chromosome. The report also suggests that without MES-4, the worm's X chromosomes may become active too early during development of the worm's reproductive tissue.

"Timing is crucial," said Strome, who led the study. "The right genes must be turned on at the right times and at the right levels. We know that the X chromosomes are kept silent during most of the germ cell development, and turning on the X chromosomes too early is probably devastating to the reproductive tissue's ability to generate sperm or egg cells."

Results from the study also show the critical role played by three other MES proteins, which like MES-4 are initially supplied to each worm embryo by its mother. The presence of these three proteins is necessary to keep MES-4 off the X chromosomes during normal embryo development. If any of the three proteins is defective or missing from the embryonic germ cells, MES-4 spreads to the X chromosomes and the X chromosomes become active, eventually resulting in a sterile adult worm.

"The embryo needs to inherit MES-4 and the other MES proteins from its mother, to create the right genetic environment in the nascent reproductive tissue," Strome said. "If the MES proteins are not loaded into the embryo, we think that the embryonic germ cells express inappropriate genes at inappropriate times."

Strome and her team previously found that defects in the gene encoding MES-4 result in adult worms that completely lack the ability to produce sperm or egg cells.

Getting the right dose of gene expression from X chromosomes appears to be a challenge for any organism that has different sexes, including humans. In the non-reproductive cells of humans, this problem is solved by inactivating one of the two X chromosomes in females, so that they resemble male cells, each of which has only one X chromosome. Worm germ cells solve the problem differently, by inactivating the single X chromosome in males and both X chromosomes in hermaphrodites.

The study was funded by a grant from the National Institutes of Health. IU biologists Youyi Fong, Laurel Bender and Wenchao Wang also contributed to the report.

Note: To arrange an interview with Strome, contact David Bricker at 812-856-9035 or