For 3 billion years, life on Earth consisted of single-celled organisms like bacteria or algae. Only 600
million years ago did evolution hit on a system for making
multicellular organisms like
animals and plants.
The key to the system is to give the cells that make up an organism a variety of different identities so that they can
perform many different roles.
So even though all the cells carry the same genome, each type of cell must be granted access to only a few of the genes in the genome, with all the others
permanently denied to it.
People, for instance, have at least 260 types of cells, each
specialized for a different tissue or organ, but presumably each type can activate only some of the 22,500 genes in the human genome.
The nature of the system that assigns cells their various identities is a central mystery of animal existence, one that takes place at the earliest moments of life when the all-purpose cells of the early embryo are directed to follow different fates. Biologists at the Broad and Whitehead Institutes in Cambridge, Massachusetts, have delved deep into this process and uncovered what seems to be a crucial
feature of how a cell's fate is
determined, even though much remains to be understood.
They have discovered a striking new feature of the chromatin, the specialized
protein molecules that protect and control the giant molecules of DNA that lie at the center of every chromosome.
The feature explains how embryonic cells are kept in a poised state so that all of the genome's many developmental programs are blocked, yet each is ready to be executed if the cell is assigned to that developmental path.
The developmental programs, directing a cell to become a neuron, say, or a liver cell, are initiated by master regulator genes. These genes have the power to reshape a cell's entire form and function because they control many lower genes.
They do so by producing
proteins known as transcription factors that bind to special sites on the DNA and control the
activity of the lower-level target genes.
A question of interest for biologists studying cell identity is what regulates the master regulator genes. The answer has long been assumed to lie in the chromatin, which determines which genes are accessible to the cell and which are excluded. The chromatin consists essentially of millions of miniature protein spools around each of which the DNA strand is looped some one and half times.
The spools, however, are not mere packaging. They can lock up the DNA they are carrying so that it is inaccessible.
Or they can unwind a little, so that the strand becomes accessible to the transcription factors seeking to copy a gene on the DNA and generate the protein it specifies.
Working backward from that knowledge, biologists have spent much effort trying to learn how the state of the spools is determined.
They have learned there are protein complexes -- essentially sophisticated cellular machines -- that travel along the
chromosome and mark the spools with chemical tags placed at
various sites on the spool.
A complex known as a polycomb -- the name comes from the anatomy of fruit flies, in which it was first discovered -- - tags spools at a site called K27.
This is a signal for another set of proteins to make the spools wrap DNA tight and keep it inaccessible.
Another complex tags spools at their K4 site, which has the opposite effect of making them loosen their hold on the DNA.
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