Researchers have discovered a protein that adjusts gene activity to match the level of nutrients in roundworms

Transforming a fertilized egg into a fully functional adult is a complex task. Cells must divide, move, and mature at a given time. Developmental genes control this process, turn it on and off in a choreographic way.

However, the environment affects development. A team of researchers led by Cold Spring Harbor Associate Professor Christopher Hammell reported on December 22, 2020 in the journal Current Biology how gene activity matches nutrient levels.

They found a main switch that worms use to stop growth when nutrients are low. When the environment improves, the animals continue to develop. The switch adjusts the activity of the gene to match the level of nutrients.

Caenorhabditis elegans is a tiny roundworm. In the laboratory, this worm develops from an embryo into an adult of 959 cells in approximately three days. Hammell says:

It always happens the same way. You always get 959 cells, and the patterns of those divisions that those cells give you are always done the same way between one animal and another. “

Christopher Hammell, Associate Professor, Cold Spring Harbor Laboratory

The genes that direct this flexible program are turned on and off in predictable patterns as the embryo transforms into a fully formed worm through several stages of the larva.

In the wild, developing worms cannot always depend on pleasant temperatures and abundant food. Sometimes development has to stop until conditions improve. Hammell’s team discovered a protein called BLMP-1 that adapts gene activity (transcription) to keep pace with development.

When the conditions are good, the level of BLMP-1 increases and reveals parts of the DNA, so that the genes are more accessible. Activators then turn on the genes at the right time.

“This is a mechanism that predicts to say‘ everything is fine, make development as robust as possible, ’” Hammell explains.If conditions are not optimal, BLMP-1 levels drop, leaving genes tightly packed, slowing or even stopping development.

The team’s experiments revealed BLMP-1 as the major regulator of thousands of genes that turn on and off during development. Hammell says it was a surprise because his team initially set out to investigate this process in only a few developmental genes. BLMP-1 is unique in that it coordinates many different types of processes.

Hammell is not the first researcher to draw attention to BLMP-1. The analog gene is known to be overactive in some human blood cancers, where it alters the activity of a large number of genes. Hammell hopes BLMP-1 will enter C. elegans will provide a model system for studying human diseases.